Hi all,
Cancer cell evasion techniques;
A quick documentary to explain some events .
https://youtu.be/e8orJ-v_-H0?si=kcEXUEOZ-q3Y1inu
1 . Hiding in plain sight".
Cancer cells use disguises like healthy cells, making them hard to spot. They do this by a few varied ways
2. Turn down visibility signals (like reducing MHC proteins, these proteins carry an ID card, if the immune system can't see it they don't attack the cancer cell), acting like a stealth mode
3. Mimic normal cells by using "don't attack me" signals that healthy cells use
4. "Sabotaging security guards"
They hijack immune system off-switches (like regulatory T-cells) to shut down attacks. Imagine cancer bribing the body's police force to stand down.
5.Stealing energy supplies"
Cancer cells use nanotubes (straw-like tunnels) to suck power from immune cells, draining their batteries while boosting themselves.
6. "Overwhelming defenses"
They grow too fast for the immune system to handle, like a zombie horde multiplying faster than soldiers can fight.
7. "Evolving escape plans"
Through immunoediting, they:
Change their appearance (mutate) to avoid detection.
Keep only sneaky versions that survived previous immune attacks
The immune system is built to fight foreign invaders (like viruses), not the body's own cells gone rogue. Cancer exploits this by:
Using insider knowledge (they're your own cells) to trick defenses
Creating a toxic neighborhood (tumor environment) that paralyzes immune cells
Real-world comparison
It's like a spy (cancer cell) who:
Wears a uniform to blend in (disguise)
Bribes guards (immune cells) to ignore them
Cuts power to security cameras (steals energy)
Recruits too many allies to arrest (rapid growth)
Ok so how do cancer cells evade CHEMOTHERAPY?
Drug Pumps: Grow molecular "sump pumps" (MDR proteins) to flush out chemo drugs out of the cancer cell. Imagine a bilge pump.
Force Fields: Activate physical forces to stabilize cell structures during treatment.
Death Switch Sabotage:
Overproduce anti-death signals (Bcl-2 proteins)
Break p53 (key "self-destruct" protein) so the cancer cells breaks this protein , maybe think the cancer stops the mechanics from doing routine maintenance on the normal cell .
Key Difference
The immune system faces disguise tactics (reduced MHC, fake "healthy" signals), while chemotherapy battles mechanical/biochemical defenses (drug pumps, DNA repair). Both ultimately exploit the tumor's ability to mutate rapidly and hijack normal cell functions.
Example
A cancer cell might:
Against immunity: Wear an "invisibility cloak" (PD-L1 protein, we shall talk about PD-L1 next part, it's important, can we use an adjunct drug with Cdh17) to trick T-cells
Against chemo: Use "scissors" (DNA repair enzymes) to undo drug damage
"Fake ID": Cancer wears a disguise to look like healthy cells
"Bribe Guards": Tricks immune cells into standing down
"Cut Camera Feeds": Hides its danger signals
"Overwhelm Security": Grows too fast to control
Against Chemo
"Drug Pumps": Installs tiny pumps to spit chemo drugs back out
"Force Fields": Reinforces cell walls against drug attacks
"Repair Crews": Fixes DNA damage from chemo overnight
Fake Death": Pretends to die, then regrows later
Key Difference
Your immune system gets tricked by lies and disguises, while chemo gets beaten by mechanical defenses (pumps, shields, repair teams). Both struggle because cancer keeps mutating - like a burglar constantly changing their tools.
https://youtube.com/shorts/mO63na-USsE?si=IY0aPGKi-e02zooZ
Real-World Comparison
Imagine:
Immune evasion = A spy using forged papers and bribes
Chemo evasion = A fortress with moats, repair workers, and secret tunnels
Here's how cancer cells dodge radiotherapy, explained simply:
1. "DNA Repair Crews"
Cancer cells activate emergency repair teams (DNA repair pathways) to fix radiation damage. These teams work overtime to stitch broken DNA back together.
2. "Sleep Mode" Trick
Some cells hit pause on multiplying (cell cycle arrest) to avoid radiation's worst effects, buying time to repair damage.
3. "Death Signal Blockers"
They overproduce survival proteins (like Bcl-2) that act as "anti-suicide shields," blocking the self-destruct commands radiation tries to trigger.
Shape-Shifting Escape"
Surviving cells sometimes morph into new forms (epithelial-mesenchymal transition) that resist treatment and spread more easily.
5. "Neighborhood Watch"
The tumor creates a toxic environment (low oxygen, protective cells) that shields cancer cells and weakens radiation's impact.
6. "Clone Army"
Radiation sometimes accidentally breeds tougher cancer cells by killing weaker ones first, leaving resistant clones to regrow.
Why This Matters
Radiation works by breaking cancer's DNA, but these tricks let tumors:
Fix breaks faster than we can cause them
Ignore death orders they should obey
Evolve stronger versions of themselves
Real-World Comparison
Imagine radiation as a bulldozer smashing a building:
Good outcome: Building collapses (cancer dies)
Evasion tactics:
Workers rebuild walls mid-demolition (DNA repair)
Reinforce structures with steel (survival proteins)
Secret tunnels let people escape (morphing cells)
Dust clouds blind the bulldozer (toxic environment)
Doctors combat this by combining radiation with other treatments to outsmart these tricks
So onto Cdh17 and how the cancers cells evade death ( apoptosis)
Antigen escape (main evasion method)
CAR T-cells target specific proteins ("antigens") on cancer cells. If the cancer stops producing this target antigen (like CD19 in blood cancers), the CAR T-cells can't "see" the tumor anymore. This is called antigen escape. While CDH17 isn't yet a CAR T-cell target in current therapies, the same principle would apply - if CDH17 were targeted, cancer cells might hide by reducing CDH17 production.
The cancer cells coat themselves in glucose to avoid the GPS tracker of the T cell.
Other evasion tricks
Even if the antigen remains:
Tumor environment: Cancers create a shield of chemicals and cells that block immune attacks.
Includes ; lactate, adenosine, reactive oxygen species, cytokines,IDO, prostaglandin E2, suffice to say they disarm some T cells by a cloaking mechanism.
Cancer cells don't exhaust themselves like the T cells do, unlike T cells, cancer cells don’t expend energy attacking immune cells – they focus on growth and survival mechanisms, thus why we administer a huge amount of T cells which populate and expand in numbers ( next part we cover that). That is fascinating.
Cell resistance: Some cancer cells ignore death signals from CAR T-cells due to broken internal machinery.
T-cell exhaustion: CAR T-cells can tire out and stop working effectively over time.
Genetic instability: Cancer cells constantly mutate, allowing them to evolve new evasion tactics rather than tire out.
Resource prioritization: Tumors hijack blood vessels and nutrients to fuel their growth, avoiding energy depletion.
Cancer cells are the castle – they don’t tire; they just build stronger walls or bribe the attackers to stand down.
This dynamic explains why cancer immunotherapies focus on reducing T cell exhaustion and disabling tumor evasion tactics.
Think of cancer treatment like putting out a wildfire:
Initial attacks (chemo/immunotherapy) kill most cancer cells.
Resistant embers (remaining cancer cells) require new strategies (e.g., combination therapies).
Bottom line: We can kill cancer cells effectively – the focus now is improving precision and durability.
Part 4 next week explains Chimeric proprietary drugs in detail.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9171538/
Kpax
(20min delay)