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:

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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).