Know your mutations; Simplifying and Demystifying Genetic mistakes that become mutations and cancers
CCA Mutation Toolkit
Mutations Simplified + Trial Navigator
The Patient Mutation Toolkit: Empowering Your Cancer Journey
Designed by those who’ve walked this path – experienced patients and caregivers – the Patient Mutation Toolkit is your gateway to understanding a critical element in cancer response: your tumor’s unique genetic makeup.
Perception Is Key: See the Reality, Not the Assumption
This toolkit enables you to see your cancer for what it is, not what you think it might be. By revealing the specific mutations in your tumor, you gain invaluable insights into your personal cancer journey and how to respond effectively.
Navigating Your Options with Precision
Each mutation listing in the toolkit links directly to relevant clinical trials, offering a starting point for targeted research. For broader exploration, our main search page allows refinements by mutation type and location – think global, not just local. While a trial might not be immediately available in your region, like Australia, don’t hesitate to reach out to trial coordinators, sponsors, or drug companies worldwide. Your oncologist can be a vital ally in this process.
Persistence Pays Off: The Landscape Is Always Evolving
Remember, the world of clinical trials is dynamic, with new breakthroughs emerging continually. Don’t be discouraged by generic responses; stay proactive and informed. With this toolkit, you’re not just a patient – you’re an informed participant in your treatment journey.
Genomic Sequencing
Search For Trials
- www.genomicfocus.com
- Roche Foundation Medicine
- www.australianclinicaltrials.gov.au/about/find
- www.beta.clinicaltrials.gov
- www.omico.com.au/prospect
Facebook Groups
Understanding the Blueprint of Life
Just like a house is built from a detailed plan, our bodies are constructed following the intricate instructions of our genes. These genes are the master blueprints of life, guiding the formation and function of every cell, from the tiniest skin cell to the most complex brain cell. Together, these cells form the organs and systems that make us who we are.
In the realm of cancer, understanding these genetic blueprints becomes crucial. Mutations – like unexpected changes in a building plan – can lead to issues in how our cells behave and function. The Patient Mutation Toolkit is your guide and starting point to deciphering these changes, empowering you to understand and navigate your treatment journey with clarity.
Remember, knowledge of your genetic makeup is a powerful tool in the fight against cancer. It’s about knowing the plan, spotting the changes, and taking informed action.
A Gold Standard Knowledge Pathway to better decision making
Being an informed patient means you understand the information in a way that you can proactively act on it to make better quality decisions. This is the first crucial step towards becoming an “Empowered Patient.”
Think of the content below, as sequential stepping stones of knowledge. Understanding this sequence will provide you with a significant advantage.
- DNA: We are all individually uniquely DNA coded. This makes us – us
- DNA Replication: Our DNA code is in continuous replication
- DNA Mistakes: Replication mistakes are common, also environmental (epigenetic) influences like the sun, chemicals, and smoking create mistakes in our DNA sequence.
- DNA Spell Checker: The immune system acts as a regulatory force, with mechanisms including DNA spell checking to repair or eliminate cells with mistakes. It also signals for repair, elimination, or cessation of attacks.
- Unrepaired Mistakes: Sometimes the Immune system can miss DNA mistakes, thus unrepaired mistakes or bad cells remain and continue to grow and multiply unchecked.
- Mutations: Unrepaired mistakes can lead to genetic mutations (tumours) and some become cancers.
- New technology detects mistakes in DNA with tests like immunohistochemical analysis and molecular profiling;
- IHC (Immunohistochemistry) is a fast and efficient laboratory technique that uses chemical staining containing antibodies to detect and display specific protein abnormalities in tissue samples.
- Molecular profiling delves deeper into the tumor’s genomic environment by using genetic tests to identify mutations, gene expression, and proteins in a tissue sample that may be driving the growth of cancer.
- Tissue samples are obtained during surgery or biopsy. If a tissue sample is not able to be obtained, blood biopsies are an alternative method used increasingly, it can also provide ctDNA information (ct = circulating tumour) this is tumour shedding material in the blood.
- Pharmaceutical companies are continuously developing immunotherapies that target the mutations 9mistakes) driving tumor growth, and providing added assistance to the immune system.
- Immune support: Our immune system can miss unrepaired mistakes in DNA, allowing cancer to grow. Targeted immunotherapy drugs provide assistance to the immune system in fighting cancer.
The most frequently observed mutations in cholangiocarcinoma are:
- IDH1 (Isocitrate Dehydrogenase 1) Mutations – Approximately 20% of intrahepatic cholangiocarcinomas (iCCAs) [VIDEO] + [VIDEO]
- IDH2 (Isocitrate Dehydrogenase 2) Mutations – Less frequent than IDH1, approximately 5% of iCCAs
- KRAS (Kirsten rat sarcoma viral oncogene homolog) Mutations – Around 5-10% of iCCAs [VIDEO] + [VIDEO]
- TP53 (Tumor Protein P53) Mutations – Around 10-35% of iCCAs [VIDEO] + [VIDEO] + [VIDEO]
- BAP1 (BRCA1 associated protein-1) Mutations – Approximately 15-25% of iCCAs
- FGFR2 (Fibroblast Growth Factor Receptor 2) Fusions – Approximately 10-15% of iCCAs
- BRAF (v-Raf murine sarcoma viral oncogene homolog B) Mutations – Less than 5% of iCCAs
- PIK3CA (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha) Mutations – Varies, but generally less than 5% of iCCAs
- SMAD4 (SMAD Family Member 4) Mutations – Less than 5% of iCCAs
Please note that these percentages can vary depending on the population studied and the specific subtypes of cholangiocarcinoma (i.e., intrahepatic, perihilar, and distal). Also, these are only the most common mutations and many other less frequent genetic changes can occur in cholangiocarcinoma.
For the most accurate and updated information, I recommend checking resources like the American Cancer Society or a medical genetics database.
In addition to the more common mutations, other less common genetic mutations and alterations seen in cholangiocarcinoma can include:
- ARID2 (AT-rich interaction domain 2) Mutations
- ACVR1B (Activin A receptor type 1B) Mutations
- BRCA1 (Breast Cancer Gene 1) Mutations
- BRCA2 (Breast Cancer Gene 2) Mutations
- ARID1A (AT-rich interaction domain 1A) Mutations
- ATM (Ataxia Telangiectasia Mutated) Mutations
- PBRM1 (Polybromo 1) Mutations
- ROS1 (ROS Proto-Oncogene 1, Receptor Tyrosine Kinase) Fusions
- ALK (Anaplastic Lymphoma Kinase) Fusions
- NTRK (Neurotrophic Tyrosine Kinase) Fusions
- MET (MET Proto-Oncogene, Receptor Tyrosine Kinase) Amplifications or Exon 14 Skipping Mutations
- ERBB2 (also known as HER2) Amplifications or Mutations
- CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) Loss or Mutations
- PTEN (Phosphatase and Tensin Homolog) Loss or Mutations
- RET (Ret Proto-Oncogene) Mutations
- CTNNB1 (Catenin Beta 1) Mutations
- NF1 (Neurofibromin 1) Mutations
- AKT1 (AKT Serine/Threonine Kinase 1) Mutations
As our understanding of cancer genomics continues to evolve, new mutations and alterations are continually being discovered. It’s important to note that the precise frequency and significance of these less common mutations can vary. Their presence can sometimes influence treatment decisions, particularly with the development of more targeted therapies. For the most accurate and up-to-date information, it’s best to consult a medical professional or a reputable genetics database.
Cholangiocarcinoma (CCA) has been reported to have one of the highest rates of potentially actionable tumor targets among all types of solid tumors. This is because of the high frequency of genetic alterations and mutations that have been identified in CCA, many of which have the potential to be targeted by specific therapies.
For example, mutations in the genes encoding isocitrate dehydrogenase 1 and 2 (IDH1/2) are found in a subset of CCA cases, and targeted therapies such as ivosidenib and enasidenib have been developed to specifically target these mutations. These drugs have shown promise in clinical trials and have been granted FDA approval for the treatment of IDH1/2-mutant cholangiocarcinoma.
Fusions in the fibroblast growth factor receptor 2 (FGFR2) gene have also been found in a subset of intrahepatic CCA cases, and several FGFR inhibitors, such as pemigatinib and infigratinib, have been developed to target these fusions. These drugs have also shown promise in clinical trials and have been granted FDA approval for the treatment of FGFR2 fusion-positive CCA.
Other potential targets for targeted therapies in CCA include mutations in genes such as BRAF, ERBB2, and NTRK, among others. However, further research is needed to determine the efficacy of targeted therapies for these mutations in CCA.
Overall, the high frequency of actionable tumor targets in CCA suggests that precision medicine approaches may be particularly promising in the treatment of this disease.
Potential therapeutic targets are like specific ‘weak points’ in cancer cells that scientists and doctors are trying to target with special treatments. These targets are often genes or proteins that have gone wrong in cancer cells, like the oncogenic driver alterations we talked about earlier. By developing medicines that can specifically block or attack these targets, doctors hope to stop the growth of cancer cells or even destroy them completely. Finding and targeting these specific weaknesses gives us a better chance of fighting against cancer and improving treatment outcomes.
- PD-L1: PD-L1 is a protein found on the surface of cancer cells that can help them evade the immune system. Checkpoint inhibitors, such as drugs that block the interaction between PD-L1 and immune cells, are being explored as potential therapeutic options for cholangiocarcinoma patients with high PD-L1 expression.
- ERBB2 (HER2): HER2-targeted therapies, such as HER2 inhibitors or antibody-drug conjugates, are being explored as potential treatment options for cholangiocarcinoma patients with ERBB2 (HER2) amplifications or mutations.
- FGFR2: Targeted therapies inhibiting FGFR2 signaling, such as FGFR inhibitors, are being investigated as potential treatment options for cholangiocarcinoma patients with FGFR2 fusions or mutations.
- FGFR1: FGFR1 inhibitors are also being explored as potential targeted therapies for cholangiocarcinoma patients with FGFR1 alterations.
- BRAF: BRAF inhibitors, which block the abnormal activity of mutated BRAF protein, are being explored as potential targeted therapies for cholangiocarcinoma patients with BRAF mutations.
- PIK3CA: Inhibitors targeting the PI3K/AKT/mTOR signaling pathway, which is often dysregulated due to PIK3CA mutations, are being investigated as potential therapeutic options for cholangiocarcinoma patients with PIK3CA mutations.
- ROS1: Targeted therapies, such as ROS1 inhibitors, are being studied as potential treatment options for cholangiocarcinoma patients with ROS1 fusions.
- ALK: ALK inhibitors, which can block the abnormal activity of ALK protein, are being explored as potential targeted therapies for cholangiocarcinoma patients with ALK fusions.
- NTRK: NTRK inhibitors are being investigated as potential targeted therapies for cholangiocarcinoma patients with NTRK fusions.
- MET: MET inhibitors, including MET tyrosine kinase inhibitors, are being studied as potential therapeutic options for cholangiocarcinoma patients with MET amplifications or Exon 14 skipping mutations.
- ERBB2 (HER2): HER2-targeted therapies, such as HER2 inhibitors or antibody-drug conjugates, are being explored as potential treatment options for cholangiocarcinoma patients with ERBB2 (HER2) amplifications or mutations.
- IDH1 and IDH2: IDH inhibitors are being studied as potential targeted therapies for cholangiocarcinoma patients with IDH1 or IDH2 mutations.
These potential therapeutic targets are based on the specific alterations observed in cholangiocarcinoma and are being actively investigated in preclinical and clinical studies to develop effective targeted therapies for patients with this disease.
Known Biomarkers for CCA
- CA19-9:
- Normal range: Typically less than 37 U/mL
- Elevated levels can indicate cholangiocarcinoma or other conditions like pancreatitis or liver disease.
- CEA:
- Normal range: Less than 5 ng/mL for non-smokers, less than 6.5 ng/mL for smokers
- Elevated levels can indicate cholangiocarcinoma or other conditions like inflammatory bowel disease or chronic liver disease.
- AFP:
- Normal range: Varies depending on the laboratory and testing method used
- Elevated levels can indicate the presence of a tumor or other conditions such as liver diseases, pregnancy, or in healthy individuals.
- CA125:
- Normal range: Typically below 35 units/mL, but may vary depending on the laboratory
- Elevated levels can indicate cholangiocarcinoma or other conditions. It is primarily used for monitoring treatment response and detecting disease recurrence.
- p53: Mutations in the p53 gene can serve as a prognostic biomarker in cholangiocarcinoma.
- Mismatch repair genes (MMR): Deficiencies in MMR genes can lead to a condition called microsatellite instability (MSI) in cholangiocarcinoma. MSI testing helps identify patients who may benefit from immunotherapy.
- MSI Status:
- MSI-High (MSI-H): Tumors that exhibit a high level of microsatellite instability.
- MSI-Low (MSI-L): Tumors that show a low level of microsatellite instability.
- Microsatellite Stable (MSS): Tumors that show no significant microsatellite alterations.
- Lynch Syndrome: Associated with mutations in certain MMR genes like MLH1 and MSH2. It increases the risk of developing several types of cancer, including cholangiocarcinoma.
- PD-L1: High levels of PD-L1 expression in tumor cells may indicate a higher likelihood of response to immunotherapies. The tumor proportion score (TPS) measures the percentage of tumor cells showing PD-L1 expression. A high TPS indicates a higher percentage of tumor cells showing PD-L1 expression.
Mutations that are also Biomarkers
In the context of cholangiocarcinoma, mutations in the following genes can serve as biomarkers:
- p53: Mutations in the p53 gene can serve as a prognostic biomarker in cholangiocarcinoma.
- Mismatch repair genes (MMR): Deficiencies in MMR genes can lead to a condition called microsatellite instability (MSI) in cholangiocarcinoma. MSI testing helps identify patients who may benefit from immunotherapy.
- Lynch Syndrome: This is associated with mutations in certain MMR genes like MLH1 and MSH2. It increases the risk of developing several types of cancer, including cholangiocarcinoma.
Remember, while these mutations can serve as biomarkers, they’re a subset of the broader category of biomarkers, which also includes proteins and other substances produced by the body in response to cancer.
Australia
- (3 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA
- (9 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
Excerpt: Invisible Cities Within.
What is IDH1:
Imagine your body’s trillions of cells as bustling cities, let’s call them Cell-Cities. Each Cell City works hard to build and maintain its infrastructure to keep everything running smoothly.
Now, let’s introduce ‘Genes.’ We have many thousands of these in our bodies, as many as 20,000 unique genes. All the genes combined form the ‘City Plan’ that guides each Cell City. You can think of each gene as a specific specialist section of the master plan. These specialist genes are located inside ‘City Hall,’ the nucleus of each cell.
Among the many genes, one important gene is called IDH1. It carries the unique and specialized blueprints for our cell’s power plant. IDH1 provides detailed instructions to the ‘City Planners’ called mRNA, on how to build a molecule called alpha-ketoglutarate. This molecule acts as the power plant, creating energy to keep the Cell City functioning optimally. Building and maintaining these power plants is a crucial operation for the city’s smooth operation.
Let’s delve into the scientific description of IDH1:
- IDH1 is a gene that provides instructions related to cell metabolism and growth. It stands for isocitrate dehydrogenase 1.
- Isocitrate, a small molecule found in our cells, helps produce energy.
- Dehydrogenase, a special protein, accelerates this energy production through chemical reactions.
- Isocitrate dehydrogenase is an enzyme that works to convert isocitrate into another molecule called alpha-ketoglutarate.
- Alpha-ketoglutarate is a molecule that plays a crucial role in cellular energy production and metabolism.
It’s important to note that IDH1 is not involved in DNA repair mechanisms or tumor suppression. Instead, it focuses on regulating cell metabolism and growth.
Understanding the functions of genes like IDH1 helps scientists and doctors study cellular processes and develop insights into diseases. By studying these genes and their instructions, they can improve our understanding of how cells work and develop better strategies for diagnosing and treating various conditions.
So what has gone wrong with my IDH1?
First, let’s take a look at what the scientists are telling us:
- Gene replication and mistakes: During the process of gene replication, mistakes can occur, leading to changes in the gene instructions.
- Factors like environmental exposures (chemicals, smoking) and random errors during replication can cause these mistakes.
Now, let’s dive back into the story to help you understand what’s happening:
One day, there’s a glitch in the city plans for the IDH1 Power Plant – a mistake in the gene’s blueprint has somehow occurred and gone unnoticed. The mRNA City Planners unaware of this mistake innocently continue delivering faulty instructions which are now building a faulty power plant, built with faulty weak proteins (Proteins are our body’s and cells’ essential building material). This new, faulty power plant begins producing strange, harmful waste (2-HG) instead of pure alpha-ketoglutarate energy, and ‘Cell City’ quickly becomes polluted, and the harmful 2-HG piles up clogging the city.
What can be done to fix our IDH1 and prevent the City from turning into a dark mutant Cell City?
First, let’s take a look at what the scientists are telling us:
- Cells have mechanisms to fix gene mistakes, acting like DNA spell-checkers and repair systems.
- These repair mechanisms constantly check for errors in the gene instructions and correct them.
- Sometimes, the DNA repair mechanisms themselves can make mistakes, preventing the proper fixing of gene errors.
Now, let’s continue the story and see what our own body is capable of:
As the harmful waste, 2-HG continues to accumulate in the city, the city’s repair mechanisms and immune response superheroes become aware of the chaos in Cell City. They activate their armies of DNA spellcheckers and rapid response genes that rush to the faulty IDH1 Power Plant. With their expert skills, they assess the situation and identify the root of the problem and discover it begins with the faulty IDH1 gene blueprint back in City Hall. (Nucleus)
City Hall’s rapid repair teams get to work, using their DNA spell-checkers to identify the mistakes in the genes blueprint instructions. They carefully repair the faulty IDH1 blueprint gene, ensuring it returns to its normal function of providing the correct instructions for the power plant and returning everything back to normal.
But sometimes the repair mechanisms may make mistakes of their own and are unable to fully fix the blueprint genes in City Hall. Despite their best efforts, the faulty power plant persists, continuing to produce harmful waste and disrupting the normal functioning of Cell City. So that’s when we have to turn for help from our superhero scientists.
What happens is our DNA repair teams can not fix the IDH1 problem?
Unrepaired gene mistakes and cancer development:
- If the repair mechanisms fail to fix errors in the IDH1 gene, the mistakes remain unrepaired.
- Unrepaired mistakes in the IDH1 gene can contribute to abnormal cell growth and the development of cholangiocarcinoma, a type of cancer in the bile ducts.
Investigating the primary contributor to the gene mutation:
- It is important to investigate the underlying causes of the gene mutation to develop personalized treatment plans.
- Understanding the specific factors contributing to the mutation helps doctors tailor treatment options accordingly.
Scientists are learning fast and are researching new treatments:
So what are the scientists saying about this?
- Scientists are actively researching IDH1 mutations in cholangiocarcinoma to develop targeted therapies.
- Targeted therapies are drugs designed to specifically target and block the effects of the mutated IDH1 protein, inhibiting its abnormal function and preventing cancer growth.
- Clinical trials are testing new treatments, including targeted therapies, for cholangiocarcinoma with IDH1 mutations.
- Participating in clinical trials can provide access to innovative treatments and contribute to advancing medical knowledge.
How can scientists help us?
Scientists love to solve puzzles and work things out, intrigued by the complexities of the IDH1 gene and its impact on cellular processes, they step in to lend their expertise. They dedicate their time and resources to understanding the specific nature of the IDH1 mutation and developing strategies to fix it.
Through their research, scientists are always discovering potential ways that can target the faulty IDH1 blueprint gene and get it back to working properly. They create special innovative drugs (medications) that can enter Cell City and then City Hall and fix the problem and stop the wrong instruction that are creating faulty power plants to stop the pile-up of toxic 2-HG waste and pollution.
Scientists and the Doctors who work with them work hard every day to save Cell City from turning into a dark mutant Cell City, scientists work hand in hand with the superheroes of repair mechanisms and immune response. Together, they strive to find effective solutions to fix the IDH1 gene and restore the city to its normal, healthy state.
Some important notes about IDH1:
- Genomic profiling of tumor tissue is performed to identify IDH1 mutations and guide treatment decisions.
- Seeking a second opinion from specialists or cancer centers with expertise in cholangiocarcinoma and IDH1 mutations may provide additional insights and treatment recommendations.
- Support groups and organizations can offer valuable support, resources, and information for patients with cholangiocarcinoma and IDH1 mutations.
- Taking care of your overall well-being by maintaining a healthy lifestyle and seeking emotional support really helps.
Specific questions to ask your oncologist about IDH1 mutations:
- Can you explain how the IDH1 gene mutation affects my cancer and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for my specific diagnosis type with IDH1 mutations?
- What are the potential benefits and risks of recommended treatment options?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- What are the potential benefits and risks of the recommended treatment options for my IDH1 mutation?
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Are there lifestyle modifications or supportive care options to improve overall well-being during treatment?
- Can you provide resources or recommend support groups for patients with IDH1-related cancers?
Remember to have open and honest discussions with your oncologist to fully understand your specific situation and explore all potential treatment options.
Other Resources
Here is a recent article of IDH1 relevance:
Australia
- (0 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA
- (3 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
What is KRAS:
Genes carry instructions to tell our cells what to do. KRAS is a gene in our cells:
- KRAS is a gene that provides instructions to our cells on how to grow and divide.
- KRAS stands for “Kirsten Rat Sarcoma” oncogene, which refers to the name given to a type of cancer called sarcoma that was initially identified in rats.
- Sarcoma is a type of cancer that affects connective tissues, such as bones, muscles, and blood vessels.
- An oncogene is a gene that, when mutated or altered, has the potential to promote abnormal cell growth and contribute to the development of cancer.
- The KRAS gene, associated with various cancers, was later named after this particular type of sarcoma.
- The KRAS gene provides instructions for making a protein called KRAS.
- The KRAS protein controls how cells grow and divide.
- KRAS is neither a DNA repair mechanism nor a tumor suppressor gene.
Gene Replication and Mistakes:
- During gene replication, mistakes can occur, leading to changes in the gene instructions.
- Mistakes can be caused by various factors such as exposure to chemicals, smoking, and random errors during the replication process.
Repair Mechanisms and Their Role:
- Our cells have mechanisms to fix mistakes in genes, like a DNA spell-checker and repair system.
- These repair mechanisms constantly check for mistakes in gene instructions and fix them.
- Sometimes, the repair mechanisms themselves can have mistakes, which can prevent proper fixing of errors in genes. This is something that should be investigated. An example of this is the MMR (Mismatch Repair Genes) malfunction, known as dMMR, which can cause mistakes to go unrepaired.
Unrepaired KRAS Mistakes and Cancer Development:
- If the repair mechanisms fail to fix errors in the KRAS gene, the mistakes in the gene instructions remain unrepaired.
- These unrepaired mistakes in the KRAS gene can cause cells to grow and divide too quickly, forming clusters of abnormal cells.
- Tumors can be either benign (non-cancerous) or cancerous (malignant) based on their ability to invade nearby tissues and spread to other parts of the body.
- Mutations in the KRAS gene can cause the KRAS protein to be constantly “on,” leading to uncontrolled cell growth and the development of cancer.
Investigating the Primary Contributor to KRAS Mutation:
- It’s important to investigate whether faulty repair mechanisms are the primary contributors to KRAS mutation.
- Understanding the underlying causes of the KRAS mutation helps doctors develop personalized treatment plans targeting specific factors contributing to the mutation.
- One example of underlying causes is when the KRAS protein gets stuck in the “on” position due to a mutation, which results in uncontrolled cell growth and the formation of tumors in the bile ducts.
Scientific Research and Treatments:
Scientists are actively researching KRAS mutations in cholangiocarcinoma to develop powerful treatments that can specifically target and attack cancer cells. These treatments include targeted therapies and immunotherapies.
- Targeted therapies: These are special drugs designed to specifically target and block the effects of the mutated KRAS protein or other molecules involved in cancer growth. They work like precision weapons, aiming directly at the cancer cells to stop their growth and spread.
- Immunotherapies: These treatments boost the power of our immune system to recognize and attack cancer cells. They help our immune system become stronger and smarter, enabling it to fight against the cancer more effectively.
Important notes about KRAS:
- KRAS mutations are relatively common in cholangiocarcinoma cases.
- Genomic profiling of tumor tissue is performed to identify KRAS mutations and guide treatment decisions.
- Seek a second opinion from a specialist or cancer center with current expertise in cholangiocarcinoma and KRAS mutations.
- Support groups and organizations can provide valuable support and resources for patients with cholangiocarcinoma.
- Taking care of your overall well-being by maintaining a healthy lifestyle and seeking emotional support really helps.
Specific questions to ask your oncologist:
- Can you explain how the KRAS gene mutation affects my cancer and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for my specific cancer type with KRAS mutations?
- What are the potential benefits and risks of recommended treatment options?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- What are the potential benefits and risks of the recommended treatment options for my KRAS mutation?
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Are there lifestyle modifications or supportive care options to improve overall well-being during treatment?
- Can you provide resources or recommend support groups for patients with BAP1-related cancers?
Remember to have open and honest discussions with your oncologist to fully understand your specific situation and explore all potential treatment options.
Other Resources
Australia
- (2 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA
- (8 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
What is an FGFR2 Gene:
Genes carry instructions to tell our cells what to do. FGFR2 is a gene in our cells:
- FGFR2 is a special gene in our cells that gives instructions for cell growth, development, and repairing tissues.
- FGFR2 stands for “Fibroblast Growth Factor Receptor 2” gene.
- Imagine FGFR2 as a receiver on the surface of our cells that receives important signals from special proteins called Fibroblast Growth Factors (FGFs).
- Fibroblast Growth Factors (FGFs) are like messengers in our body, telling our cells when to grow, divide, and do important tasks for our body’s development and health.
- Our own cells produce Fibroblast Growth Factors (FGFs) and release them into our body to talk to other cells and organs.
- The “2” in FGFR2 represents a specific subtype or version of the receptor protein called FGFR.
- It’s like having different flavors of the same protein, and each subtype has its own job in cell communication.
- So, when we talk about FGFR2, we are talking about one particular subtype that has its own unique role in our cells.
- FGFR2 is neither a DNA repair mechanism nor a tumor suppressor gene.
Gene replication and mistakes:
- When our genes are being copied (replicated), mistakes often occur leading to changes in the gene instructions.
- These mistakes can also occur due to various factors like environmental exposures such as chemicals, smoking, and other random errors that impact the replication process.
- Sometimes, changes or mistakes can happen in the FGFR2 gene, and these changes are called mutations.
- These mutations can lead to problems like uncontrolled cell growth, forming tumors, and causing cancer.
Repair mechanisms and their role:
- Our cells have mechanisms to fix these mistakes, like a DNA spell-checker and repair system.
- These repair mechanisms constantly check for mistakes in the gene instructions and fix them.
- However, sometimes the repair mechanisms themselves can have mistakes, preventing them from properly fixing the errors in the gene. This is something that should also be investigated. An example of this is MMR (Mismatch Repair Genes) can sometimes malfunction and this is known as dMMR (deficient) this malfunction can cause mistakes to go unrepaired. This is something that should be known and discussed with your Oncologist.
Unrepaired FGFR2 mistakes and cancer development:
- If the repair mechanisms are unable to fix the errors in the FGFR2 gene, the mistakes in the gene instructions remain unrepaired.
- These unrepaired mistakes in the FGFR2 gene can cause the cells to grow and divide too quickly, leading to the formation of clusters of abnormal cells (tumors).
- Tumors can be either benign (non-cancerous) or cancerous (malignant) depending on their ability to invade nearby tissues and spread to other parts of the body.
- A benign tumor means that the cells are abnormal but do not spread to other parts of the body. It usually does not pose a serious threat to health.
- On the other hand, a cancerous tumor also called a malignant tumor, means that the cells have the ability to invade nearby tissues and spread to other parts of the body, potentially causing harm and disrupting the normal functioning of organs.
Investigating the primary contributor to FGFR2 mutation:
- Investigating the primary contributor to FGFR2 mutation: As a patient with an FGFR2 mutation, it’s crucial to investigate the primary contributor to the mutation, including potential rare biomarkers such as MMR (Mismatch Repair) or MSI-high (High Microsatellite Instability) that may be associated with the mutation, even though they are rare occurrences.
- Additionally, assessing the expression of PD-L1, which can indicate the potential response to immunotherapy, should also be considered.
- Understanding the underlying causes of the FGFR2 mutation, including the presence of rare biomarkers and PD-L1 expression, helps doctors develop personalized treatment plans that take into account all possible factors contributing to the mutation.
Fibroblast:
- A fibroblast is a special type of cell found in our body’s connective tissues, like skin, tendons, and organs.
- Fibroblasts have an important job in building and maintaining the structure of these tissues.
Growth Factor:
- A growth factor is a natural substance in our body that helps cells grow, divide, and do their specific jobs.
- It’s like a special signal that tells cells when and how to grow and develop.
Receptor:
- Think of a receptor as a cell’s “receiver” or “detector.”
- Receptors are like antennas on the surface of a cell that can pick up signals from other molecules, like growth factors.
- When a ‘fibroblast‘ growth factor molecule attaches to the receptor, it sends a message inside the cell to start certain processes, like cell growth and division.
Scientific research and treatments:
- Scientists are actively researching FGFR2 mutations and developing targeted therapies.
- Targeted therapies aim to block the activity of the mutated FGFR2 protein and inhibit cancer cell growth.
- Clinical trials are evaluating the effectiveness and safety of targeted therapies for FGFR2-mutated cancers.
Important notes about FGFR2:
- Genomic profiling helps identify FGFR2 mutations and guide treatment decisions.
- Seeking a second opinion from a specialist or cancer center with expertise in FGFR2 mutations is recommended.
- Support groups and organizations can provide valuable support and resources for patients with FGFR2-mutated cancers.
- Taking care of your overall well-being by maintaining a healthy lifestyle and seeking emotional support is important during treatment.
Specific questions to ask your oncologist:
- Can you explain how the FGFR2 gene mutation affects my cancer and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for my specific cancer type with FGFR2- mutations?
- What are the potential benefits and risks of recommended treatment options?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- What are the potential benefits and risks of the recommended treatment options for my FGFR2 mutation?
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Are there lifestyle modifications or supportive care options to improve overall well-being during treatment?
- Can you provide resources or recommend support groups for patients with FGFR2-related cancers?
Remember to have open and honest discussions with your oncologist to fully understand your specific situation and explore all potential treatment options.
Currently no trials
Let’s help you understand what TP53 is and how it relates to your condition:
What is a TP53 Gene:
Genes carry instructions to tell our cells what to do. TP53 is a gene in our cells:
- TP53 is a gene in our cells that provides instructions for making a protein called p53.
- p53 is a superhero protein that protects our cells from turning into cancer.
- It acts as a guardian, making sure cells grow and divide properly and preventing them from becoming abnormal.
- TP – Tumor Protein
- What is a Suppressor Gene:
- Suppressor genes are like superheroes in our bodies that fight against cancer.
- They act as DNA guardians, ensuring cells stay healthy and preventing harmful changes.
- Tumor Suppressor Genes, like TP53, are the second line of defense against cancer, stopping it in its tracks.
- TP53 is also known as “P53” because the protein it makes weighs about 53 kilodaltons, which is a measure of its size.
Gene Replication and Mistakes:
- When our genes are copied, mistakes can occur, leading to changes in the gene instructions.
- These mistakes can happen due to various factors like environmental exposures or errors in the replication process.
Repair Mechanisms and Their Role:
- Our cells have repair mechanisms, like a DNA spell-checker and repair system, that fix mistakes in the gene instructions.
- These repair mechanisms constantly check for mistakes and fix them to ensure the genes work properly.
- However, sometimes the repair mechanisms themselves can have mistakes, making it harder for them to fix gene errors.
Unrepaired TP53 Mistakes and Cancer Development:
- If mistakes in the TP53 gene are not fixed, they can contribute to abnormal cell growth and increase the risk of cancer.
- Mutations in the TP53 gene can disrupt its tumor suppressor function, which helps prevent cancer development.
Investigating the Primary Contributor to TP53 Mutation:
- It’s important to investigate the main cause of TP53 mutations, such as faulty repair mechanisms or other factors.
- Understanding the underlying causes of TP53 mutations helps develop personalized treatment plans and preventive measures.
Scientific Research and Treatments:
- Scientists are researching TP53 mutations to develop treatments that specifically target cancer cells with TP53 alterations.
- These treatments may include targeted therapies and innovative approaches to restore normal TP53 function.
Important Notes about TP53:
- TP53 mutations are associated with an increased risk of several types of cancer, including breast, colorectal, lung, and ovarian cancer.
- Genomic profiling of the tumor can provide valuable information about specific alterations or biomarkers associated with TP53 mutations, guiding treatment decisions.
- Seek a second opinion from a specialist or cancer center with current expertise in TP53 mutations for optimal management.
Specific Questions to Ask Your Oncologist:
- Can you explain how the TP53 gene mutation affects my cancer and what it means for my treatment options?
- Are there any targeted therapies or clinical trials available for my specific type of cancer with TP53 mutations?
- How does the TP53 mutation impact the choice of treatment options and their effectiveness?
- Are there any additional surveillance or preventive measures recommended due to the TP53 mutation and the increased risk of other types of cancer?
- Does my genomic profile indicate any other specific alterations or biomarkers that could impact treatment decisions for TP53-mutated cancer?
- What are the expected outcomes and prognosis for my specific type of cancer with TP53 mutations?
- Are there any support groups or resources available for patients with TP53-mutated cancers that can provide additional information and support throughout my treatment journey?
Remember to have open and honest discussions with your oncologist to fully understand your specific situation and explore all potential treatment options.
Currently no trials
What is a BAP1 Gene:
BAP1 is a gene in our cells: Genes carry instructions to tell our cells what to do.
- The BAP1 gene provides instructions for making a protein called BAP1 (BRCA1-associated protein 1).
- BAP1 stands for “BRCA1-associated protein 1.”
- BAP1 is a gene that encodes the BRCA1-associated protein 1. Associated means they work very closely together.
- BRCA1 stands for “Breast Cancer Susceptibility Gene 1.”
- BAP1 is like a superhero in our cells, helping to keep them healthy and prevent the development of cancer.
- It does this by repairing any mistakes or abnormalities in our DNA, which is like the instruction manual of our cells.
- BAP1 is classified as a tumor suppressor gene, and its protein product acts as a surveillance mechanism within the cell. It helps in identifying and repairing errors or abnormalities in DNA. By detecting and correcting DNA errors, BAP1 helps maintain the integrity of the genome and prevent the development of cancerous cells.
- Scientists are studying BAP1 to better understand how it works and to develop ways to help people with BAP1 mutations stay healthy and prevent cancer.
- BAP1 is a tumor suppressor gene.
Gene Replication and Mistakes:
- Our genes, like instruction manuals, are copied or replicated to make new cells.
- Sometimes, mistakes or changes can happen during this copying process, similar to errors in a recipe.
- These mistakes can occur due to different factors, like exposure to chemicals or even random errors that happen naturally.
Repair Mechanisms and Their Role:
- Our cells have special mechanisms that act like spell-checkers and repair systems for genes.
- These repair mechanisms constantly check for mistakes in the gene instructions and fix them, just like correcting errors in a text.
- However, sometimes these repair mechanisms can also have their own mistakes, which can prevent them from fixing gene errors properly. This is something that scientists are still investigating.
Unrepaired BAP1 Mistakes and Cancer Development:
- If the mistakes in the BAP1 gene are not fixed by the repair mechanisms, they can cause problems in the cell.
- These mistakes disrupt the normal function of the BAP1 protein, which can affect important processes in the cell.
- Unrepaired mistakes in the BAP1 gene can lead to uncontrolled cell growth and division, like cells that keep multiplying without control.
- This uncontrolled growth can form clusters or masses of abnormal cells called tumors.
- There are different types of tumors: benign tumors that stay in one place and do not spread, and cancerous tumors that can invade nearby tissues and spread to other parts of the body, causing harm.
Investigating the Primary Contributor to BAP1 Mutation:
- To understand why the mistakes in the BAP1 gene happen, scientists study different factors that could be involved.
- Some factors include inherited genetic predisposition, which means the gene mistake is passed down from parents, and environmental exposures, like things in the environment that could cause gene changes.
- Investigating the primary contributor to a BAP1 mutation helps doctors create personalized treatment plans and surveillance strategies tailored to each individual.
Scientific Research and Treatments:
- Ongoing research aims to better understand BAP1 mutations’ role in cancer development.
- Targeted therapies and treatment approaches are being explored to specifically target cancer cells with BAP1 alterations.
Important Notes about BAP1:
- BAP1 mutations are associated with an increased risk of certain cancers, such as mesothelioma and uveal melanoma.
- Genomic profiling can identify BAP1 mutations and guide treatment decisions.
Specific Questions to Ask Your Oncologist:
Very Important questions to all tumor types in Cholangiocarcinoma:
These questions relate to a wider range of treatment options, especially targets and immunotherapies
- Does my genomic profile indicate higher levels of PD-L1, which can be associated with immune evasion by cancer cells?
- Does my genomic profile indicate MSi-high (High microsatellite instability), which can indicate a potential response to immunotherapy?
- Is my genomic profile indicating TMB-High (High level of tumor burden loading), suggesting a higher number of gene mutations in my tumor?
BAP1 Specific Questions:
- Can you explain how the BAP1 gene mutation affects my cancer and treatment options?
- Are there targeted therapies or clinical trials available for my specific cancer type with BAP1 mutations?
- What are the potential benefits and risks of recommended treatment options?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- What are the expected outcomes and prognosis for my cancer type with BAP1 mutations?
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Are there lifestyle modifications or supportive care options to improve overall well-being during treatment?
- Can you provide resources or recommend support groups for patients with BAP1-related cancers?
Australia
- (0 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA / ALL
- (7 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
What is a BRAF Gene:
BRAF is a gene in our cells that provides instructions for making a protein called BRAF.
- The BRAF gene is like a recipe book inside our cells.
- It contains the instructions to make a protein called BRAF, which helps control how cells grow and divide.
- BRAF got its name from a type of cancer called fibrosarcoma, but it’s more well-known for its role in another type of cancer called melanoma.
More;
- BRAF stands for “B-Rapidly Accelerated Fibrosarcoma” gene.
- Fibrosarcoma is a type of cancer that originates from fibrous connective tissue, such as tendons, ligaments, and deep layers of the skin. It is characterized by the uncontrolled growth of malignant fibroblast cells. Fibrosarcoma can occur in various parts of the body, including the limbs, trunk, and head and neck region. It is considered a rare type of cancer.
- Fibroblast cells are specialized cells involved in producing and maintaining the structural framework of tissues and organs in the body.
- The BRAF gene is neither a repair mechanism or a tumor suppressor gene.
Gene Replication and Mistakes:
- When genes are copied, mistakes can occur, like errors in a recipe, leading to changes in the gene instructions.
- In the case of the BRAF gene, these mistakes can make the BRAF protein work too much, like a gas pedal stuck in the “go” position, causing cells to grow and divide too quickly.
- These changes and rapid cell growth can contribute to the development of cancer, especially in melanoma.
Repair mechanisms and their role:
- Our cells have repair mechanisms that act like DNA spell-checkers and fix mistakes in the gene instructions.
- These repair mechanisms constantly check for errors and fix them to ensure the genes work properly.
- However, sometimes the repair mechanisms themselves can have mistakes, which can prevent them from fixing the errors in the gene. This should be investigated and discussed with an oncologist.
Unrepaired BRAF mistakes and cancer development:
- If the repair mechanisms cannot fix the mistakes in the BRAF gene, the errors remain unrepaired.
- These unrepaired mistakes can cause cells to grow and divide too quickly, forming clusters of abnormal cells called tumors.
- Tumors can be either benign (not spreading) or cancerous (spreading to other parts of the body) depending on their behavior and the potential harm they can cause.
Investigating the primary contributor to BRAF mutation:
- As a patient with a BRAF mutation, it is important to investigate the main cause of the mutation, such as faulty repair mechanisms or other factors.
- Understanding the underlying causes of the BRAF mutation can help doctors make informed treatment decisions and create personalized treatment plans.
Scientific research and treatments:
Scientists are actively researching BRAF mutations to develop targeted therapies that specifically address cancers with BRAF alterations. These treatments aim to inhibit the abnormal activity of the mutated BRAF protein and slow down or stop the growth of cancer cells.
Here are several examples of strategies used to inhibit the function of the mutated BRAF protein:
- BRAF Inhibitors: Small molecule inhibitors have been developed to specifically target and block the activity of the mutated BRAF protein. These inhibitors bind to the mutated protein, preventing its activation and downstream signaling, which can help to control the growth of cancer cells.
- Combination Therapies: BRAF inhibitors are often used in combination with other drugs to enhance their effectiveness. For example, combining a BRAF inhibitor with a MEK inhibitor, which targets a protein downstream of BRAF, can lead to more potent inhibition of the signaling pathway and improved clinical outcomes.
- Immunotherapies: Immunotherapeutic approaches, such as immune checkpoint inhibitors, are being explored in combination with BRAF inhibitors. This combination aims to enhance the immune system’s ability to recognize and attack cancer cells with BRAF mutations.
- Precision Medicine: With advances in genomic profiling and personalized medicine, efforts are being made to identify specific genetic alterations accompanying BRAF mutations. This information helps in developing individualized treatment strategies that target multiple components of the signaling pathway involved in BRAF-driven cancers.
It’s important to note that treatment approaches may vary depending on the specific type of cancer and the presence of additional genetic alterations. Clinical trials and ongoing research continue to investigate new treatment combinations and approaches to further improve outcomes for patients with BRAF-mutated cancers.
Important notes about BRAF:
- BRAF mutations are less common in cholangiocarcinoma compared to other cancers like melanoma and colorectal cancer.
- When BRAF mutations occur in cholangiocarcinoma, they may be associated with a more aggressive tumor behavior.
- Genomic profiling of tumor tissue is important to identify BRAF mutations and guide treatment decisions.
- Targeted therapies that specifically target BRAF mutations, such as BRAF inhibitors, are being investigated for their effectiveness in cholangiocarcinoma.
- Participation in clinical trials and discussions with knowledgeable healthcare providers can provide access to emerging treatments and personalized care options tailored to your BRAF mutation status.
Specific questions to ask your oncologist:
These questions relate to a wider range of treatment options, especially targets, and immunotherapies
- Does my genomic profile indicate higher levels of PD-L1, which can be associated with immune evasion by cancer cells?
- Does my genomic profile indicate MSi-high (High microsatellite instability), which can indicate a potential response to immunotherapy?
- Is my genomic profile indicating TMB-High (High level of tumor burden loading), suggesting a higher number of gene mutations in my tumor?
BRAF-Specific Questions:
- Can you explain how the BRAF gene mutation affects my cholangiocarcinoma and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for cholangiocarcinoma with BRAF mutations?
- What are the potential benefits and risks of the recommended treatment options for my specific case?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- Are there any specific considerations or modifications in lifestyle that can improve my overall well-being during treatment?
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Can you provide resources or recommend support groups for patients with BRAF-mutated cholangiocarcinoma?
Remember to have open and honest discussions with your oncologist to fully understand your specific situation and explore all potential treatment options.
Australia
- (0 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA/All
- (2 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
What is a PIK3CA Gene:
Genes carry instructions to tell our cells what to do. PIK3CA is a gene in our cells:
- The PIK3CA gene is like an instruction manual inside our cells.
- It contains the information to make a special protein called PIK3CA.
- Think of the PIK3CA protein as a traffic controller inside the cell, directing cell growth and division.
- Just like a traffic controller on the road, the PIK3CA protein makes sure cells grow and divide at the right times and in the right amounts.
So, the PIK3CA gene and protein are like important regulators in the cell, making sure everything happens in the right order. But when there are changes in the gene, it’s like having a traffic controller that doesn’t know when to stop, and that can cause problems like cancer.
The PIK3CA gene is not a repair mechanism or a tumor suppressor gene.
Gene Replication and Mistakes:
- Sometimes, changes can happen in the PIK3CA gene, like a typo in the instruction manual.
- These changes can make the PIK3CA protein too active, like a traffic controller signaling cells to grow and divide too much.
- This can lead to the formation of tumors and the development of cancer.
Repair mechanisms and their role:
- Cells have repair mechanisms that fix mistakes during gene replication, including those in the PIK3CA gene.
- These mechanisms act like DNA spell-checkers, constantly checking for mistakes in the gene instructions and fixing them.
- They help maintain the integrity of DNA and ensure the proper functioning of the PIK3CA protein.
Unrepaired PIK3CA mistakes and cancer development:
- If mistakes in the PIK3CA gene are not fixed properly, they can build up and cause problems.
- Unrepaired PIK3CA mutations can disrupt normal cell processes and lead to uncontrolled cell growth, increasing the risk of cancer.
- Sometimes, the DNA spell-checkers themselves become mutated, preventing them from fixing errors in the genes. This should be investigated, especially the mismatch repair genes (MMR) that can malfunction and leave mistakes unrepaired.
Investigating the primary contributor to PIK3CA mutation:
- It is important to investigate and understand the primary contributor to PIK3CA mutations, such as faulty repair mechanisms or other factors.
- Identifying the underlying causes of the PIK3CA mutation can help guide treatment decisions and the development of personalized treatment plans.
Scientific research and treatments:
- It’s important to investigate if the repair mechanisms, like MMR, are working correctly in cholangiocarcinoma diagnosis.
- Understanding how these repair mechanisms function and identifying any failures can help in developing better treatment approaches for patients.
Important notes about PIK3CA:
- PIK3CA mutations are found in a subset of intrahepatic cholangiocarcinoma (iCCA) cases, generally less than 5%.
- Genomic profiling of tumor tissue is performed to identify PIK3CA mutations and guide treatment decisions.
- Seeking a second opinion from a specialist or cancer center with current expertise in PIK3CA mutations is advisable.
- Support groups and organizations can provide valuable support and resources for patients with PIK3CA-mutated iCCA.
Specific questions to ask your oncologist:
- Can you explain how the PIK3CA gene mutation affects my cancer and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for iCCA with PIK3CA mutations?
- What are the potential benefits and risks of the recommended treatment options for my specific case?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Are there any lifestyle modifications or supportive care options that can improve my overall well-being during treatment?
- Can you provide resources or recommend support groups for patients with PIK3CA-mutated iCCA?
Australia
- (0 Trials) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
USA/All
- (1 Trial) Last updated 18 May 2023
- Go to Results
- Use the print icon on the results page to download a pdf (or print)
Learn More about SMAD4:
Genes carry instructions to tell our cells what to do. SMAD4 is a gene in our cells:
- The SMAD4 gene is like a master conductor in our cells, making sure everything is in harmony.
- It produces a protein that helps cells communicate and make important decisions, like when to grow, differentiate (become specialized), or even sacrifice themselves if needed.
- The SMAD4 protein is part of a pathway called TGF-β, which is like a set of instructions that cells follow to stay balanced and work together.
- TGF-β is like a messaging system, sending signals to cells and telling them what to do. It’s important for cell growth, development, and making sure everything is functioning properly.
- SMAD4 got its name from its role in the body structure development of fruit flies (imagine a tiny conductor organizing an orchestra of cells).
- SMAD4 is a gene, specifically a tumor suppressor gene.
So, the SMAD4 gene and protein are like conductors and messengers, making sure cells work together and make the right decisions. They help maintain balance and prevent problems like uncontrolled cell growth that can lead to cancer.
Gene Replication and Mistakes:
- When our genes are copied, mistakes can happen and affect the SMAD4 gene’s DNA sequence.
- These mistakes can occur due to various factors like chemicals or random errors during the copying process.
- These mistakes can impact how the SMAD4 gene works and its role in the cell.
Repair Mechanisms and their Role:
- Cells have repair mechanisms to fix mistakes made during gene replication, including those in the SMAD4 gene.
- These repair mechanisms act like DNA “spell-checkers” and help maintain the integrity of DNA.
- They constantly check for mistakes in the gene instructions and fix them.
Unrepaired SMAD4 Mutations and Cancer Development:
- If mistakes in the SMAD4 gene are not properly repaired, they can accumulate and disrupt normal cell processes.
- Unrepaired SMAD4 mutations can lead to uncontrolled cell growth and increase the risk of cancer.
- Sometimes, the repair mechanisms themselves can become mutated and fail to fix errors, like a “spell-checker” that stops working correctly.
- Investigating these repair mechanism failures, such as the example of Mismatch Repair Genes (MMR), should be an important step in understanding cholangiocarcinoma.
Remember, our cells have built-in mechanisms to fix mistakes, but sometimes these mechanisms can also be affected. Investigating these failures is crucial for understanding and treating cholangiocarcinoma.
Investigating the Primary Contributor to SMAD4 Mutation:
- It is important to investigate and understand the underlying and primary causes of SMAD4 mutations, such as faulty repair mechanisms or other factors.
- Identifying the primary contributor to SMAD4 mutations can help guide treatment decisions and the development of personalized treatment plans.
Scientific Research and Treatments:
Scientists are actively researching SMAD4 mutations to gain insights into their impact on cancer development and explore potential targeted therapies. Understanding the specific alterations in SMAD4 can help in the development of tailored treatment approaches.
Important Notes about SMAD4:
- SMAD4 mutations are frequently found in pancreatic cancer, as well as other cancer types, including cholangiocarcinoma.
- It is important to undergo genomic profiling of tumor tissue to identify SMAD4 mutations and determine the appropriate treatment strategies.
- Seeking a second opinion from a specialist or cancer center with current expertise in SMAD4 mutations is advisable.
- Support groups and organizations can provide valuable support and resources for patients with SMAD4
Specific Questions to Ask Your Oncologist:
- Can you explain how the SMAD4 gene mutation affects my cancer and what it means for my treatment options?
- Are there targeted therapies or clinical trials available for my cancer with SMAD4 mutations?
- What are the potential benefits and risks of the recommended treatment options for my specific case?
- Are there other genomic alterations or biomarkers detected in my tumor, such as dMMR (Deficient Mismatch Repair), MSI-high (High microsatellite instability), TMB-high (High level of tumor burden loading), or high levels of PD-L1, that could provide targeted or immunotherapy options? Please note that “No” is not a suitable answer. It is strongly advised that you receive and keep a copy that shows the actual findings and scores.
- Are there any ongoing research studies or investigational treatments that may be suitable for my condition?
- Can you provide resources or recommend support groups for patients with SMAD4-mutated cancers?
Remember, this content is in a simplified format and may need to be further customized based on your specific requirements or target audience preferences.
Categories
Grouping by Types and Relationships
Biomarkers that are also Mutations
- IDH1 and IDH2 mutations
- FGFR2 fusions or mutations
IDH1/IDH2 mutations and FGFR2 fusions/mutations can be considered both biomarkers and mutations.
In the context of cholangiocarcinoma (bile duct cancer), the roles of the IDH1/IDH2 mutations and FGFR2 fusions/mutations as both biomarkers and mutations are significant:
A biomarker, on the other hand, is a broad term referring to a measurable indicator of some biological state or condition. Biomarkers are often used in cancer diagnosis, prognosis, and treatment selection.
- IDH1 and IDH2 mutations: In cholangiocarcinoma, mutations in IDH1 or IDH2 are observed in about 10-20% of cases. (often quoted as 25%) These mutations are usually found in intrahepatic cholangiocarcinomas (those occurring within the liver), and they are associated with specific characteristics and outcomes. As a biomarker, the presence of IDH1/IDH2 mutations can provide valuable information about the potential course of the disease and its possible response to targeted therapies, like IDH inhibitors.
- FGFR2 fusions or mutations: These genetic alterations are particularly important in cholangiocarcinoma. Approximately 10-15% of intrahepatic cholangiocarcinomas have FGFR2 gene fusions. The presence of these fusions can have implications for treatment, as they may predict response to targeted therapies that inhibit the FGFR pathway.
Thus, in cholangiocarcinoma, both IDH1/IDH2 mutations and FGFR2 fusions/mutations are critical pieces of the puzzle. They provide insights into the biology of the cancer and can influence treatment decisions by indicating which targeted therapies might be most effective. They can also potentially offer information about prognosis. Therefore, these mutations act both as biological drivers of the cancer and as biomarkers that can guide treatment.
Mutations:
- IDH1
- IDH2
- FGFR2
- KRAS mutations
- TP53 mutations
- BAP1 mutations
- PBRM1 mutations
- ARID1A mutations
- SMAD4 mutations
Intrahepatic Cholangiocarcinoma is a type of cancer that starts in the bile ducts inside the liver. Bile ducts are like tiny tubes that carry bile, a fluid that helps with digestion. When there are changes or mutations in certain genes, like IDH1, IDH2, FGFR2, KRAS, TP53, BAP1, PBRM1, ARID1A, or SMAD4, it can lead to the development of this cancer. Scientists and doctors study these genes and mutations to understand how the cancer grows and find potential ways to treat it. By learning more about Intrahepatic Cholangiocarcinoma and its genetic changes, we can develop better strategies to fight against it and improve patient outcomes.”
Imagine you’re a detective trying to solve a mystery called cholangiocarcinoma. To crack the case, you need clues that can give you important information about the disease. In this case, the clues are called biomarkers and mutations.
Biomarkers are like specific fingerprints that help us identify if cholangiocarcinoma is present or how it is progressing. They are special characteristics or molecules that act as evidence, pointing us in the right direction. These biomarkers can be found in the body and can provide important information for doctors to diagnose the disease, predict how it may develop, and make decisions about the best treatment options.
On the other hand, mutations are like secret codes hidden within our DNA. Our genes have an instruction manual that guides our cells’ behavior. But sometimes, mistakes happen in this manual, and these mistakes are called mutations. In the case of cholangiocarcinoma, these mutations occur in the DNA of certain genes and can have a big impact on the development and behavior of the disease.
So, biomarkers and mutations are like valuable clues in the investigation of cholangiocarcinoma. They help doctors understand the disease better, make accurate diagnoses, predict how it may progress, and decide on the most effective treatment strategies. By studying these clues, doctors can have a clearer picture of the disease and offer personalized care to their patients.
Biomarkers that are also Mutations
- MCL1 amplifications
- ERBB2 (HER2) amplifications
Both of these serve biomarkers and mutations in the context of cholangiocarcinoma. These genetic changes in the MCL1 and ERBB2 (HER2) genes indicate specific alterations associated with the disease.
Mutations:
- MCL1
- HER2
- KRAS
- TP53
- BAP1
- PBRM1
- ARID1A
- SMAD4
Notes:
Biomarkers are specific characteristics or molecules used to indicate the presence or progression of a disease. MCL1 amplifications and ERBB2 (HER2) amplifications or mutations are examples of biomarkers. Mutations refer to changes in the DNA sequence of genes, including mutations in KRAS, TP53, BAP1, PBRM1, ARID1A, and SMAD4. These mutations provide important information for diagnosis, prognosis, and treatment decisions in Extrahepatic Perihilar Cholangiocarcinoma.
Extrahepatic Perihilar Cholangiocarcinoma is a type of cancer that originates in the bile ducts outside the liver, near the hilum area. Bile ducts are small tubes that carry bile, a fluid aiding in digestion. Genetic changes or mutations in genes such as KRAS, TP53, BAP1, PBRM1, ARID1A, SMAD4, MCL1, or ERBB2 can contribute to the development of this cancer. Scientists and doctors study these genes and mutations to understand how the cancer grows and explore potential treatments. By advancing our knowledge of Extrahepatic Perihilar Cholangiocarcinoma and its genetic changes, we can develop more effective strategies to fight the disease and improve patient outcomes.
Biomarkers that are also Mutations
- FGFR2 fusions or mutations
Mutations:
- FGFR2
- KRAS
- TP53
- BAP1
- PBRM1
- ARID1A
- SMAD4
- BRAF
Notes:
FGFR2 fusions or mutations serve as a biomarker in Extrahepatic Distal Cholangiocarcinoma. Biomarkers are specific characteristics or molecules that can be used to indicate the presence or progression of a disease. The remaining mutations, including KRAS, TP53, BAP1, PBRM1, ARID1A, SMAD4, and BRAF mutations, are alterations or changes in the DNA sequence of genes. These mutations provide important information for diagnosis, prognosis, and treatment decisions in Extrahepatic Distal Cholangiocarcinoma.
Extrahepatic Distal Cholangiocarcinoma is a type of cancer that starts in the bile ducts outside the liver, in the distal or far end of the ducts. Bile ducts are like tiny tubes that carry bile, a fluid that helps with digestion. Changes or mutations in genes like KRAS, TP53, BAP1, PBRM1, ARID1A, SMAD4, FGFR2, or BRAF can be involved in the development of this cancer. Scientists and doctors study these genes and mutations to understand how the cancer grows and find potential ways to treat it. By learning more about Extrahepatic Distal Cholangiocarcinoma and its genetic changes, we can develop better strategies to fight against it and improve patient outcomes.
ATM (Ataxia Telangiectasia Mutated) – The First Responder:
Involved in about 5-10% of cholangiocarcinoma cases.
ATM rushes to DNA damage like a first responder to an accident scene. It detects issues like DNA double-strand breaks and calls in the repair crew. When ATM’s off duty, the chances of mutations rise, leading to possible cancer development.
BRCA1/2 – The Construction Crew
Involved in less than 5% of cholangiocarcinoma cases.
Think of BRCA genes as the construction experts. They get the alert from ATM and roll in to fix DNA damage. Their absence or malfunction can lead to errors, creating a breeding ground for cancer.
MDM2 (Mouse Double Minute 2):
Rare but noteworthy in cholangiocarcinoma research.
Imagine our cells have a Police Chief named p53, who makes sure everything’s running smoothly and safely. MDM2 is like a supervisor who sometimes argues with the Police Chief. When they clash, it’s like the Police Chief gets distracted and can’t do his job properly. This can lead to problems in the cell, like damage that isn’t fixed, which might cause cancer.
Mismatch Repair (MMR) Genes:
This section includes comprehensive details of the 4 genes involved in mismatch repair, highlighting their importance in maintaining genetic stability.
- MLH1 (MutL Homolog 1): This gene encodes a protein crucial for DNA mismatch repair, correcting errors during DNA replication and preventing mutations. Mutations in MLH1 may lead to an increased risk of cholangiocarcinoma by allowing genetic errors to accumulate.
- MSH2 (MutS Homolog 2): MSH2 works with MSH6 or MSH3 to identify and repair mismatched DNA. Its proper function is vital in maintaining DNA integrity, and dysregulation can contribute to cholangiocarcinoma development.
- MSH6 (MutS Homolog 6): This gene collaborates with MSH2 to recognize and bind to DNA errors, assisting in repair. Defects in MSH6 can impair this process and potentially increase susceptibility to cholangiocarcinoma.
- PMS2 (Postmeiotic Segregation Increased 2): Partnering with MLH1, PMS2 is essential for the final step of mismatch repair. Mutations in PMS2 can hinder this crucial function, leading to DNA errors that may contribute to the onset of cholangiocarcinoma.
- MSH3 (MutS Homolog 3): MSH3 binds with MSH2 to repair insertion/deletion loops (IDLs) during DNA replication. A defect in MSH3 could allow these errors to persist, playing a role in the development of cholangiocarcinoma.
Relevance to Cholangiocarcinoma:
Mutations in these genes can cause a condition known as microsatellite instability (MSI), leading to an accumulation of unrepaired DNA errors. In the context of cholangiocarcinoma, this can increase the risk of cancer development and affect the response to certain treatments. Understanding these genetic factors may guide personalized treatment strategies, offering insights into prognosis and potential therapeutic interventions specific to each patient’s genetic profile.
By familiarising themselves with these repair mechanisms, patients and their healthcare providers can make informed decisions related to screening, treatment, and management of cholangiocarcinoma, based on their unique genetic landscape.
Tumor Suppressor Genes are like the second line of defense in our bodies against cancer. They work alongside DNA Repair Mechanisms to keep our cells healthy and prevent them from becoming cancerous. Tumor Suppressor Genes act as the guardians, ensuring that cells grow and divide properly and stopping any abnormalities or potential dangers in their tracks
Tumor Suppressor genes:
- APC (Adenomatous Polyposis Coli): Regulates cell growth and division in the colon lining, mutations in this gene increase the risk of colorectal cancer.
- ARID1A (AT-rich interaction domain 1A): Controls gene expression and is involved in DNA repair, mutations in this gene are found in various cancers, including cholangiocarcinoma.
- ARID2 (AT-rich interaction domain 2): Regulates gene expression and is involved in chromatin remodeling, mutations in this gene are associated with an increased risk of several cancers.
- BAP1 (BRCA1-Associated Protein 1): Regulates cell growth and prevents tumor development, mutations in this gene increase the risk of several cancers.
- BRCA1 (Breast Cancer Gene 1): Participates in DNA repair, mutations in this gene increase the risk of breast, ovarian, and other cancers.
- BRCA2 (Breast Cancer Gene 2): Involved in DNA repair, mutations in this gene increase the risk of breast, ovarian, and other cancers.
- CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A): Acts as a tumor suppressor by inhibiting cell cycle progression, mutations in this gene are associated with an increased risk of several cancers.
- CDKN2B (Cyclin-Dependent Kinase Inhibitor 2B): Regulates cell cycle progression and suppresses tumor growth, alterations in this gene are associated with various cancers.
- FRS2 (Fibroblast Growth Factor Receptor Substrate 2): Transmits growth signals within cells, alterations in this gene have been observed in certain cancers.
- MYC (MYC Proto-Oncogene): Controls cell growth and division, alterations in MYC contribute to the development of many cancers.
- PTEN (Phosphatase and Tensin Homolog): Regulates cell growth and division, mutations or loss of PTEN function increase the risk of several types of cancer.
- SMAD4 (Mothers Against Decapentaplegic Homolog 4): Plays a role in regulating cell growth and differentiation, mutations in SMAD4 are associated with an increased risk of various cancers.
- STK11 (Serine/Threonine Kinase 11): Regulates cell growth and division, mutations in this gene are linked to the development of certain cancers.
- TP53 (Tumor Protein 53): Often called the “guardian of the genome,” it helps prevent abnormal cell growth and maintains DNA integrity, mutations in TP53 are found in many types of cancer.
- ACVR1B (Activin A receptor type 1B): Participates in cell signaling pathways, mutations in this gene have been associated with cholangiocarcinoma and other cancers.
Mutations in these genes can lead to the loss or reduction of their tumor-suppressing functions, which can contribute to the development and progression of cancer, including cholangiocarcinoma.
Oncogenic driver alterations are like the ‘troublemakers’ in our cells that can lead to cancer. They are changes or mutations in specific genes that make them work differently than they should. These alterations can ‘drive’ or push cells to grow and divide too much or in an uncontrolled way, which can lead to the development of cancer. While our DNA Repair Mechanisms and Tumor Suppressor Genes act as our body’s defense system against cancer, oncogenic driver alterations can sometimes bypass these defenses and cause problems. Understanding these alterations is important because it helps scientists and doctors develop targeted treatments to stop their harmful effects and fight against cancer.
Oncogenic driver alterations are specific genetic changes or mutations that play a crucial role in the development and progression of cancer. Here is a comprehensive list of oncogenic driver alterations observed in cholangiocarcinoma:
- KRAS: KRAS mutations are commonly observed in cholangiocarcinoma and are considered oncogenic driver alterations. They result in the abnormal activation of the KRAS protein, promoting uncontrolled cell growth and tumor development.
- BRAF: BRAF mutations are oncogenic driver alterations found in a subset of cholangiocarcinoma cases. These mutations lead to the abnormal activation of the BRAF protein, contributing to cell proliferation and tumor formation.
- NRAS: NRAS mutations are another type of oncogenic driver alteration observed in cholangiocarcinoma. These mutations affect the NRAS gene, leading to the abnormal activation of the NRAS protein and promoting tumor growth.
- MET: MET amplifications or mutations are oncogenic driver alterations seen in cholangiocarcinoma. They result in the abnormal activation of the MET receptor tyrosine kinase, which plays a role in cell growth and survival, contributing to tumor development.
- ROS1: ROS1 gene fusions are considered oncogenic driver alterations in cholangiocarcinoma. These fusions involve the rearrangement of the ROS1 gene, leading to the abnormal activation of the ROS1 protein and promoting tumor growth.
- NTRK (NTRK1, NTRK2, NTRK3): NTRK gene fusions involving NTRK1, NTRK2, or NTRK3 are oncogenic driver alterations found in a subset of cholangiocarcinoma cases. These fusions result in the abnormal activation of the NTRK protein, promoting cell proliferation and tumor formation.
- RET: RET mutations are oncogenic driver alterations in cholangiocarcinoma. When mutated, structural changes in the RET protein can cause it to activate on its own, bypassing the need for its natural growth factor, GDNF. This rogue activation instructs the whole cell to grow and divide uncontrollably.
It’s important to note that while these alterations are observed in cholangiocarcinoma, they may not be present in all cases. Additionally, the frequency and prevalence of these alterations may vary among different subtypes and stages of cholangiocarcinoma. Further research and molecular profiling studies are ongoing to identify additional oncogenic driver alterations and their therapeutic implications in cholangiocarcinoma.
Epigenetics Regulators are like a set of switches that turn genes on or off without changing the actual DNA sequence. Imagine your DNA as a recipe book; epigenetics determines which recipes are used, altered, or ignored. This can affect how cells work and is crucial in health and disease.
- DNMT3A: Adds a tiny chemical tag (Methylation) to DNA. This tag can turn genes on or off, kind of like a switch. When DNMT3A doesn’t work right, these switches might get flipped incorrectly, impacting cell behavior and potentially leading to cancer.
- EZH2: Acts like a gatekeeper, deciding which parts of our DNA are shut off. If EZH2 is faulty, it might close or open the wrong gates, disrupting normal cell functions.
- HDACs: They work like cleaners, removing specific chemical tags from proteins around DNA. These tags usually help keep DNA tightly packed and genes off. If HDACs go haywire, they might disturb this balance, affecting how genes are used in the cell.
- TET2: It’s like an eraser, removing chemical tags from DNA. This helps in turning certain genes on. If TET2 is broken, these tags might not be erased properly, leading to unusual gene activity.
Did you know? In the world of genetics, methylation, the process of adding a chemical group to DNA, is like a secret code that controls genes. This code can turn genes on or off without changing the DNA itself. It’s fascinating because this tiny change can have a big impact on how our bodies work and even influence our health. Methylation is an essential part of our biological makeup, playing a key role in everything from development to disease prevention.”
A simplified explanation for understanding Microsatellite Instability (MSI) and Deficient Mismatch Repair (dMMR):
- Microsatellite Instability (MSI): This is a condition that occurs when the DNA’s mismatch repair system (MMR) doesn’t work properly. The MMR system’s main job is to correct errors that happen when DNA is copied during cell division. When this system is faulty, errors accumulate, leading to instability in certain DNA regions known as microsatellites.
- MSI-High (MSI-H): Cells with a high level of microsatellite instability have a severely impaired MMR system, leading to an increased mutation rate. MSI-H is found in several cancers, and these cancers may respond well to certain immunotherapies.
- MSI-Low (MSI-L): Cells with a low level of microsatellite instability have a slightly impaired MMR system. MSI-L cancers often behave more like MSS cancers and are less likely to respond to certain immunotherapies.
- Microsatellite Stable (MSS): These cells do not have microsatellite instability, meaning their MMR system is functioning correctly.
- Deficient Mismatch Repair (dMMR): This term is used when the MMR system is not working correctly, leading to an accumulation of errors in the DNA. dMMR is often associated with a high mutation rate and is synonymous with MSI-H. The terms are used interchangeably in the context of cancer, particularly colorectal cancer.
Understanding MSI and dMMR can help guide treatment decisions, particularly when considering immunotherapies.
Storifying
Invisible Cities Within; A journey to Cell City.
This is an ongoing project as time permits.
Preamble: ‘Invisible Cities Within; A Journey to Cell City’ is an ongoing project framed around Mum and Dad reading a story to their 12-year-old about what’s causing their cancer. This storybook concept decodes and demystifies science into relatable characters, making the complex simple. Here’s the kicker at the centre of the concept: ‘What stands in the way becomes the way.‘ In this narrative, cancer mutations are an obstacle and an opportunity. Their presence makes us think and see what we could not before – they reveal new possibilities. Once we see these, we can team up to make them our reality. This isn’t just a story for understanding; it’s a tool for empowerment. The concept highlights that Life is composed of obstacles, and a cancer mutation is just one of those obstacles, but it can also be a new opportunity. This concept isn’t just a story; it’s a key part of ‘The Process,’ of breaking down the obstacles by shining a spotlight directly on them to see the possibilities and how we the triumph over cancer. By redefining mutations or mistakes as obstacles and opportunities emerge. It’s not just surviving the obstacle, but thriving and in control – we’re transcending to new, higher realities.
Welcome to your ‘Invisible Cities Within’ Patient Knowledge Guide.
This is a unique tool designed to simplify complex biological concepts into an easy-to-understand city analogy. As a newly diagnosed cancer patient, it’s crucial to comprehend your body’s ‘inner universe.’ This guide aims to demystify your journey, making sense of what’s happening inside your body, from normal cells to rogue cities (cancer cells), and how treatments work. By using this guide, you’ll be better equipped to participate in conversations and decision-making about your health and treatment options. Remember, understanding is the first step to empowerment.
The Human Body (Our Universe):
This is where everything takes place. It’s a vast space, full of life and activity, just like a busy universe.
Organs (Our Countries):
Each organ is like a country. They have their own specific roles but work together for the greater good of the universe – the human body.
Biological Systems (Our Regions or States):
These are the specific functional areas within our body (country), such as the digestive system, respiratory system, nervous system, etc. Each has a unique role and contributes to the overall well-being of the body. For instance, the GI tract (digestive system) is one such region responsible for processing and absorbing nutrients from food.
Cells (The Cities Within – approx 30 trillion):
These are the basic building blocks of life, much like cities are the building blocks of a country. Each cell has a unique role in the body, collectively forming a bustling universe of countries and regions (ie GI Tract, etc) with approximately 30 trillion cities.
Nucleus (The City Hall):
This is the control center of the cell. It’s where all the important decisions are made and where the city’s blueprints (genes) are stored.
Genes (The City’s Master Blueprints – approx 20,000):
These are the instructions for building and running the city. There are approximately 20,000 blueprints that determine how the city looks and functions.
DNA (The City’s Constitution or Archive):
This is the archive where all the city’s blueprints (genes) are stored. It’s the basis for everything that happens in the city.
mRNA (City Planners):
These are the guys that read the city’s blueprints (genes) and turn them into reality. They help guide the construction of the city’s workers (proteins).
Ribosomes (The City’s Protein Factories):
This is where the mRNA City Planners deliver their instructions on what needs to be built according to the instructions from the specific blueprint (gene) they work for.
Proteins (The City’s Infrastructure or Building Blocks):
These are the results of the city’s building plans. They are the infrastructure or building blocks that perform all the necessary tasks to keep the city running smoothly.
Mitochondria (The Power Plants):
These structures generate the energy for the city. They keep the lights on and power all the city’s activities.
Endoplasmic Reticulum (The Industrial Zone):
This is where a lot of the city’s workers (proteins) are made. It’s a bustling area full of activity.
MMR (The City Health Department’s Elite DNA Spellchecker and Repair Team):
This specialized team operates under the umbrella of the City Health Department. They ensure the city’s building plans (genes) are error-free and that structural integrity is maintained. They play a crucial role in maintaining the integrity of the city.
- MLH1 (The Oversight Auditor), MSH2 (The Error Spotter), MSH6 (The Detail Checker), PMS2 (The Repair Specialist): These roles are the key players who make sure the city’s blueprints are correctly followed, and any mistakes are promptly fixed.
Tumor Suppressor Genes: The City Zoning and Building Regulations
Tumor suppressor genes act like the zoning laws and building regulations in our cellular city. These rules guide the orderly growth of the city (cell proliferation) and prevent uncontrolled expansion or chaotic development (tumors). When changes or breaches occur in these regulations (gene mutations), it can disrupt the smooth operation of the city, escalating the risk of urban decay or chaos (cancer). Here’s a lineup of some of these crucial city regulations and their roles:
- TP53 (also known as p53): Acting as the chief city planner, TP53 upholds the integrity of the city by preventing the growth of unregulated buildings (abnormal cells) and maintaining the city plans (DNA).
- BRCA1 and BRCA2: These are zoning laws specifically associated with certain districts (breast and ovarian cells). Any changes or breaches in these regulations can significantly raise the risk of uncontrolled development in these areas (cancers).
- PTEN: PTEN serves as a critical city development guideline that regulates city expansion and division. Alterations in PTEN are linked with escalated risk of chaotic development in various city districts (breast, prostate, and colorectal cancer).
- APC: APC is a specific regulatory guideline for the growth of residential complexes in the colon district. Any breaches in this regulation often result in uncontrolled growth, leading to decay in the area (colorectal cancer) and other parts of the city.
- RB1: RB1 is akin to a city bylaw that controls the pace of city development, preventing over-speedy growth and division. Changes in RB1 can lead to unchecked growth, increasing the risk of decay in certain areas (retinoblastoma and other cancers).
- NF1, CDH1, VHL: These are specific regulations linked to different aspects of city development — from growth control (NF1) and building integrity (CDH1) to infrastructure development (VHL). Any changes in these regulations can increase the risk of various urban development issues (tumors).
- ATM: ATM acts like the city’s disaster management department, playing a crucial role in repairing damaged city plans (DNA) and ensuring city stability. Changes in ATM can lead to an increased risk of certain development issues, including infrastructure decay (cholangiocarcinoma).
- SMAD4: The SMAD4 regulation controls city development and is involved in various city planning processes. Any alterations can contribute to uncontrolled growth in several city areas (pancreatic and colorectal cancer).
This group of zoning laws and building regulations helps maintain the orderly function and growth of our cities (cells). They ensure everything develops according to plan, thus preserving the harmony and health of our city (body).
Oncogenic Driver Alterations (Corrupt City Officials or Rogue Architects):
Oncogenic driver alterations are like the ‘troublemakers’ in our cells that can lead to cancer – they are similar to corrupt city officials or rogue architects who bend or break the rules for their own gain. They introduce changes or mutations in specific genes that disrupt the normal functioning of the city. These alterations can ‘drive’ or push the city into chaotic and dangerous growth, bypassing the City Health Department’s defenses and other protective measures. Understanding these rogue elements is crucial for developing targeted interventions to halt their harmful effects and restore order. While our DNA Repair Mechanisms and Tumor Suppressor Genes act as our body’s defense system against cancer, oncogenic driver alterations work to bypass these defenses and cause problems. Understanding these alterations is important because it helps scientists and doctors develop targeted treatments to stop their harmful effects and fight against cancer.
Oncogenic driver alterations are specific genetic changes or mutations that play a crucial role in the development and progression of cancer. Here is a comprehensive list of oncogenic driver alterations observed in cholangiocarcinoma:
- KRAS: KRAS mutations are commonly observed in cholangiocarcinoma and are considered oncogenic driver alterations. They result in the abnormal activation of the KRAS protein, promoting uncontrolled cell growth and tumor development.
- BRAF: BRAF mutations are oncogenic driver alterations found in a subset of cholangiocarcinoma cases. These mutations lead to the abnormal activation of the BRAF protein, contributing to cell proliferation and tumor formation.
- NRAS: NRAS mutations are another type of oncogenic driver alteration observed in cholangiocarcinoma. These mutations affect the NRAS gene, leading to the abnormal activation of the NRAS protein and promoting tumor growth.
- MET: MET amplifications or mutations are oncogenic driver alterations seen in cholangiocarcinoma. They result in the abnormal activation of the MET receptor tyrosine kinase, which plays a role in cell growth and survival, contributing to tumor development.
- ROS1: ROS1 gene fusions are considered oncogenic driver alterations in cholangiocarcinoma. These fusions involve the rearrangement of the ROS1 gene, leading to the abnormal activation of the ROS1 protein and promoting tumor growth.
- NTRK (NTRK1, NTRK2, NTRK3): NTRK gene fusions involving NTRK1, NTRK2, or NTRK3 are oncogenic driver alterations found in a subset of cholangiocarcinoma cases. These fusions result in the abnormal activation of the NTRK protein, promoting cell proliferation and tumor formation.
It’s important to note that while these alterations are observed in cholangiocarcinoma, they may not be present in all cases. Additionally, the frequency and prevalence of these alterations may vary among different subtypes and stages of cholangiocarcinoma. Further research and molecular profiling studies are ongoing to identify additional oncogenic driver alterations and their therapeutic implications in cholangiocarcinoma.
Cancer Cells: Rogue Cities (Outlaw Cities or Rebel States within the Country):
Think of Germline Cells as ‘heritage cities,’ passing down traditional architecture (genes). Somatic Cells are ‘modern cities,’ always changing and more prone to ‘urban decay’ (cancer).
Sometimes, a city turns its back on the usual rules, acting like an outlaw city or a rebel state within the country. It goes rogue, changing its structures and growing uncontrollably. In biological terms, these are cancer cells. They divide and grow without regard for the well-being of the country (organ) or the universe (body). In fact, about 80% of these rogue cities are ‘Somatic,’ making them highly susceptible to going off the rails.
- Somatic Cells (The Developed Cities): Think of these as the evolving cities that adapt and change based on their environment and life experiences. Being more exposed to the world, they’re the ones most likely to undergo epigenetic changes and potentially turn into rogue cities. You could also view them as our human hardware (yes like a computer)
- Germline Cells (The Founding Cities): These are the cells that develop over time. They adapt and change based on their environment and experiences. Being more exposed to the world, they’re the ones most likely to undergo epigenetic changes and potentially turn into rogue cells. Consider them as the out-of-the-box computer hardware like the CPU, keyboard, and monitor.
- Epigenetic changes are like “software updates” for our cells. They don’t change the DNA sequence but affect how genes are read or expressed. These modifications can be triggered by various factors like diet, stress, or environmental exposures, and they can play a role in many diseases like cancer. It’s another layer of complexity on top of our genetic code.
Tissues (The City Districts and Infrastructure): Think of tissues as the various districts within our cities, such as residential, commercial, and industrial areas. These districts have different roles but are all essential parts of the city’s overall infrastructure, like roads, bridges, and utilities.
Urban Sprawl (Tumor Formation): These rogue cities can grow into a large, chaotic urban sprawl – analogous to a tumor. This uncontrolled growth can put pressure on the nearby cities, affecting their ability to function properly.
Blood (The Highway System):
Blood is the highway system that carries nutrients, oxygen, and waste to and from our cities.
- Invaders (Metastasis): Occasionally, some inhabitants of these rogue cities decide to explore new lands. They travel via roads or rivers (bloodstream or lymphatic system) and start new rogue cities in other parts of the country or even in different countries (metastasis).
Hormones (Postal Service or Messenger):
These are the body’s messengers, delivering important messages from one part of the body to another. They help in coordinating the body’s activities.
Cytokines (Emergency Broadcast System):
These are special proteins that are produced when there’s an infection or inflammation. They send out emergency signals, alerting the body’s defense system.
Antigens (City’s Flags or Emblems):
These are unique markers produced and displayed on the surface of cells, acting like city flags or emblems. In healthy situations, these markers are recognized as ‘self’ or friendly by the immune system, indicating that the cell is a natural part of the body. However, when a cell becomes infected or undergoes changes, such as in cancer, these markers can change. These new or altered flags are seen as ‘non-self’ or foreign, triggering the immune system to take action. They signal whether a city (cell) belongs to the country (body) or is an intruder.
Immune System (The Police Force):
The immune system acts as a police force, protecting our cities from harmful invaders.
- City Defense and Renovation (Treatment): To deal with these rogue cities, the universe (body) and its countries (organs) have some defense mechanisms, like the police force (immune system). However, sometimes, this is not enough, and external help is needed. This is where medical interventions come in. Treatments like surgery can be seen as a demolition crew, physically removing the rogue cities. Chemotherapy and radiation therapy act like a strict city administration imposing harsh rules that particularly affect the rogue cities, aiming to halt their chaotic growth. Immunotherapy is like equipping the police force with better weapons to fight the rogue cities.
- Regulatory Department: This is the universe, country, and city defense and regulatory force. It protects our body’s universe from invaders and keeps everything in check, with the power to activate or deactivate cellular functions.
- T-Cells (Elite Law Enforcement): These are the special forces of the body’s defense department. They’re trained to spot and eliminate threats to the body.
- Checkpoint Pathway (Border Patrol/FBI/CIA): This system ensures that all the cells are cooperating peacefully. It keeps an eye out for cells that are not following the rules.
- PD-1 and PD-L1, CTLA-4 (Checkpoint Officers and City’s Passports): These officers verify the identities of the cells. They make sure every cell is who it claims to be and is doing its job.
- Immunotherapy (Special Training for Defense Department): This is a special training program for the body’s defense department. It helps them identify and neutralize threats more effectively.
- BRCA1/BRCA2 (City’s Building Code Inspectors): These are genes that produce proteins responsible for repairing damaged DNA. In their inspector role, they help prevent the development of rogue cities (cancer cells).
Mutations (Rogue Workers or Saboteurs):
These are changes in the city’s building plans. Some of them can be harmful, leading to the creation of rogue workers that cause problems in the city. They are mistakes left unchecked or missed by the immune system.
Cancer Cells (Rogue Cities):
These are cities that have gone rogue. They don’t follow the rules, causing problems for the whole body (universe). These rogue cities often arise from mutations that were not corrected.
Metastasis (Rogue Cities Colonizing Other Countries):
When rogue cities (cancer cells) start to spread and establish colonies in other parts of the universe (the body), it’s a process called metastasis. It’s a serious situation that needs immediate attention.
Chemotherapy (Airstrikes):
This is a form of treatment that involves using powerful drugs (airstrikes) to destroy rogue cities (cancer cells). Unfortunately, it can also harm some of the good cities in the process.
Radiotherapy (Precision Strikes):
This treatment uses high-energy particles or waves, like X-rays, to target and destroy rogue cities (cancer cells) without causing much damage to the surrounding good cities.
Targeted Therapy (Elite Sniper Team):
This is a newer type of cancer treatment that uses drugs or other substances to precisely identify and attack rogue cities (cancer cells), causing less harm to normal cities (cells).
Biomarkers (City Health Indicators):
These are like the city’s health check-up report. They can indicate how well a city is functioning and if there are any problems.
Cancer Staging (Threat Level Assessment):
This refers to the process of determining the size of a rogue city (cancer) and how much it has spread. It helps in planning the right strategy to fight the rogue cities.
Oncologist (War Strategist):
This is a doctor who specializes in treating cancer. They’re the strategist who plans and oversees the campaign against rogue cities (cancer cells).
Antibodies (Immune System’s Detectives):
These are produced by the immune system in response to antigens. They act like detectives, identifying and binding to specific antigens, marking them for destruction by the immune system. They’re key players in the body’s defense against foreign substances. Some forms of immunotherapy (Special Training for the Defense Department) work by producing large numbers of these detectives, or by designing synthetic ones, to better equip the immune system to recognize and destroy rogue cities (cancer cells).
DNA Repair Mechanisms in Cell City
Welcome to Cell City, where everything is humming along smoothly—thanks to some unsung heroes who keep the city’s DNA blueprint safe and sound. Let’s meet them:
Think of DNA repair mechanisms as the City Health Department, equipped with emergency services like firefighters and EMTs. They’re responsible for keeping the city structurally sound and stepping in for urgent repairs and inspections. This team ensures that building plans (genes) are properly followed and that any structural issues (DNA damage) are swiftly addressed, preventing the city from going rogue or collapsing.
ATM – The First Responder
- Involved in about 5-10% of cholangiocarcinoma cases.
When something goes wrong in Cell City’s DNA, ATM is the first to show up—just like a fireman. ATM signals for help and gets the repair crew moving. If ATM’s on a break, Cell City’s DNA can get messy, and that’s not good.
BRCA1/2 – The Construction Crew
- Rarely involved, but super important.
These are the builders and fixers. They get a call from ATM and start repairing broken DNA. If they slack off, Cell City might face some serious issues, like cancer.
MDM2 – The Watchful Supervisor
- Rare but keeps showing up in research.
MDM2 is kinda like the boss who doesn’t always get along with the top cop of the city, named p53. When MDM2 messes around, it makes it hard for p53 to do its job, which could lead to big trouble in Cell City.
Mismatch Repair (MMR) Genes – The Quality Control Team
This crew keeps an eye on the city’s DNA blueprint, always looking for errors and fixing them. Meet the team:
- MLH1: The boss of Quality Control. He catches common mistakes.
- MSH2: The keen-eyed inspector, flags anything that looks off.
- MSH6: Works closely with MSH2 to double-check things.
- PMS2: Gives the final okay to any corrections made.
- MSH3: Handles the tricky stuff, like fixing broken roads or pipes.
If this team messes up, the city’s DNA gets all jumbled, causing problems like cancer.
So, there you have it—Cell City’s secret protectors. If they don’t do their job right, we have to bring in real-life superheroes like doctors and scientists to save the day!
Got questions? It’s cool to ask the experts—like your mum’s doctor—what’s going on with these DNA heroes in her specific case.
And that’s how Cell City stays in tip-top shape—or gets back on track when things go sideways.
Although this appears in the Story version, it is important to further highlight this to Cholangiocarcinoma patients when newly diagnosed. Only a small percent of CCA patients will benefit from this, but it is extremely important that you be sure to know if you qualify for Checkpoint Immunotherapy.
The Checkpoint Pathway: The Body’s Immune System Policing Super Pathway Ensuring Our Cellular DNA Functions Correctly
Just as a country has an established system to police its cities and ensure order, our bodies have a system known as the checkpoint pathway. This pathway functions as part of our country’s (body’s) immune system, overseeing the operations of all our cellular cities. It ensures that cells behave as they should and keeps an eye out for cities that have outlived their life expectancy or have gone rogue, such as in the case of cancer.
Two key agencies in this system are PD-1 and PD-L1. Think of these two as special envoys whose job is to maintain peaceful cooperation among cells. PD-1 is found on the surface of T-cells, the patrolling units of our cellular cities, and PD-L1 is expressed by other cells. When PD-1 on T-cells interacts with PD-L1 on other cells, it’s like a peaceful handshake, signaling that all is well and the cell can continue to function normally.
Unfortunately, rogue cities (cancer cells) can misuse this peaceful handshake. These cells overexpress PD-L1, fooling the T-cell patrollers into thinking they’re friendly, which allows them to continue their chaotic activities undetected.
This is where modern medicine steps in. Immunotherapy treatments, specifically PD-1 or PD-L1 inhibitors, act like enhanced training for our T-cell patrollers. These treatments block the misleading handshake between PD-1 and PD-L1, effectively revealing the true nature of the rogue cities (cancer cells). With this knowledge, our T-cell patrollers can now recognize these miscreants and neutralize them.
In essence, the checkpoint pathway is a crucial aspect of our country’s (body’s) immune system policing. By ensuring proper cellular behavior and identifying rogue cities (cancer cells), this pathway plays a significant role in maintaining the overall health of our country (body). By understanding and manipulating this pathway, we can devise more effective strategies to combat diseases like cancer.
- Did you know our bodies consist of over 30 trillion cells? It’s like 30 trillion tiny cities running our country, the human body.
- We carry about 20,000 genes, which serve as our body’s master blueprint.
- ‘Germline’ mutations are inherited, like a family legacy, present in every cell of our body from birth.
- ‘Somatic’ mutations occur after birth, affecting only some cells. It’s like some cities changing their rules over time.
- Around 80% of cancers arise from these ‘somatic’ mutations, making them the usual suspects in the detective story of cancer.
- Cancer is a twofold problem: a genetic issue because it changes our genes, and a metabolic issue because it disrupts how our cells use energy and nutrients. It’s like a criminal who changes city rules (genes) and causes power outages (metabolism).
- The “chicken or the egg” question applies here: Does a gene mutation cause metabolic changes leading to cancer, or do metabolic changes cause the gene mutations that result in cancer? It’s an ongoing debate in cancer research. Currently, many scientists focus on genetic mutations first, but this may not be the whole story. Understanding this can open new avenues for cancer therapies.
- The rate at which cells renew themselves varies greatly depending on the type of cell. Here’s a general idea:
- Red blood cells: Every 120 days.
- Skin cells: Approximately every 2-3 weeks.
- Liver cells: About once a year.
- Intestinal cells (excluding the lining): Approximately every 2-4 days.
- Intestinal cells (the lining, or epithelial cells): Every 4-5 days.
- Fat cells: About 10% are renewed each year.
- Bone cells: The entire human skeleton is thought to be replaced every 10 years.
It’s fascinating to think that many parts of your body may be much ‘younger’ than you are! Let’s include this information in the bullet point:
- Cells in our body regularly renew themselves, just like cities often rebuild and renovate. For example, your skin cells renew every 2-3 weeks, red blood cells every 120 days, and your entire skeleton is replaced roughly every 10 years. It’s a constant cycle of renewal and regeneration!
AAA
Spotlight on RET:
- What Is It? RET stands for “Rearranged During Transfection.” Despite the complicated name, it’s a gene that helps with cell growth and division.
- Why Should You Care? When RET is mutated, it can contribute to certain types of cancer, including cholangiocarcinoma.
- Fun Fact: RET was discovered by accident during a science experiment. Sometimes, big breakthroughs happen when you least expect them!