An undead city under siege, soldiers and police ruthlessly shooting down waves of zombies that flood from infected streets, trying to escape and infect more cities. This is what happens when your body fights cancer, more exciting than any movie. How does this battle for survival unfold?
- The Elimination Phase It all begins with a single corrupted cell. It is no longer able to repair its genetic code, it can’t kill itself anymore and it is beginning to multiply rapidly. At this point things are not great, not terrible – this cell is not yet dangerous but if nothing happens, it soon will be. Over a few weeks the corrupted cell keeps making copies of itself. One cell turns into dozens, hundreds, thousands. Because the original was broken, its copies are breaking and mutating even more. They turn into different genetic lineages, clans that are working together and competing. Some mutate in a way that makes them weaker, others’ mutations don’t change anything, while a few become fitter and better at survival. Together they now form a tiny, tiny tumor. Not cancer yet, but getting there.
The growing tumor needs a lot of resources. If the cells don’t get food and oxygen, they will die and the problem just solves itself. Unfortunately a few corrupted cells unlock a new mutation that saves them: The ability to order the growth of new blood vessels. And so your body provides the supply they need to survive. But as the tumor continues to grow, it starts causing damage – neighbouring healthy cells begin to starve and die, which attracts attention. In a sense this tiny tumor is like a rogue town. Imagine a group of rebels in Brooklyn decided that they were no longer part of New York but started a new settlement called Tumor Town, which happens to occupy the same space. The new city wants to grow, so it orders tons of steel beams, cement and drywall. New buildings follow no logic, are badly planned, ugly and dangerously crooked. They are built right in the middle of streets, on top of playgrounds and on existing infrastructure. The old neighbourhood is torn down or overbuilt to make room for new stuff. Many of the former residents are trapped in the middle of it and begin to starve.
This goes on for a while until the smell of death finally attracts attention. Building inspectors and police show up. In your body, attracted by the stench of dead cells your immune system is activated. First responder immune cells invade the tumor: Macrophages and Natural Killer Cells, police forces that go right to work, killing and eating tumor cells. They release chemical signals that let the whole immune system know that there is cancer to be eradicated. Dendritic Cells, the intelligence officers of your immune system, collect samples of dead tumor cells and begin activating your heavy weapons: Helper and Killer T Cells. We explained these specialized super weapons in another video, but all you really need to know is that they have a library listing every bad thing that could come into your body. While each cancer is unique, there are genetic corruptions that they can’t hide. And your T Cells know what to look for. They are the deadliest cancer killers you have.
By the time they arrive, the tumor has grown to hundreds of thousands of cells, but this is about to change. T Cells block the growth of new blood vessels, which starves thousands of tumor cells and puts an end to their growth. Imagine the building inspectors, switching off electricity and water and putting up roadblocks to cancertown so no more food and materials can be delivered. With no way to hide from the carnage unfolding, the tumor collapses as hundreds of thousands of tumor cells are massacred. Their carcasses are cleaned up and consumed by Macrophages that then order healthy tissue to regenerate. Your body has crushed the illegal Tumor Town without mercy. You will never know about this fight or how many times this has happened inside your body. Except… in this case something did not go as planned.
The Equilibrium Phase Unfortunately, natural selection spoils your victory. By doing its best to destroy the tumor, your immune system accidentally selects the fittest tumor cells. Remember, the tumor consists of different lineages that keep growing and keep mutating. Most of these are eradicated. But just a few are more resilient. One cell survives – it comes from the fittest tumor lineage and was just a bit better at surviving the massacre than anyone else. It decides to do it all over again. But better this time. This tumor cell is much stronger than any of the thousands that were killed. Maybe it is better at hiding, or fighting back. Maybe it grows faster or is better at stealing resources. Maybe it can survive with much less oxygen. And so it all begins again. It’s like the surviving rebels that started Tumor Town have learned their lessons. Now they know the law better and how to break it, what permits help them, how to avoid the police.
And so the surviving tumor cell makes thousands of copies that mutate and form new lineages, until once again a tumor has grown, made up from more resilient cells. The immune system does not care though, and this time it even has experience - instead of starting with police, swat teams go right in to tear Tumor Town down, killing its inhabitants without mercy. But once again they don’t get everyone. One of them survives: a fitter tumor Cell from an already fitter lineage. This time it gets a cheap suit and studies the building code, pretending to be a lawyer to start Tumor Town all over again.
This struggle now repeats a few times, each time the rebels learn a bit more about how to avoid the law. If at any point, the immune system gets all of the tumor cells, the story ends. But in this case, it doesn’t. Finally, a tumor cell changes in a way that makes it properly dangerous, cancer. The type that kills people.
How? Immune cells have an off switch that deactivates them before they can attack – which in principle is a good idea. The immune system is extremely dangerous and in many cases it needs to be shut down, like around your central nervous system. But this off switch can be exploited. The mutated tumor cell finds a way to switch the immune system off by targeting inhibitor receptors on anti cancer cells. Inhibitor receptors stop immune cells from, well, killing. This cell is the now powerful founder of a new lineage of cancer cells and mass produces thousands of new copies that once again change and mutate further. Building yet another Tumor Town.
The Escape Phase The new cancer cells have become immune to the immune system and everything is different this time. Tumor Town has been rebuilt, even uglier and stranger than before, but now the cancer city council has forged all sorts of permits. As building inspectors come to shut down construction, they get confused. Stunned they wander off, unable to order the destruction of the sprawling buildings. Police try to enter the illegal city to arrest the builders and execute inhabitants – but this time Tumor Town has erected its own roadblocks that keep the law from entering. Confused officers stand around helplessly.
As Tumor Town slowly envelops the former Brooklyn and more and more civilians die, T Cell swat teams arrive to end this travesty. But things got worse – new lineages of Tumor Town officials have started to forge court documents that order police to shoot at the Swat teams. What the cancer cells are doing at this point is actively shutting down immune defenses by sending corrupt signals. The now malignant tumor is no longer a pushover and has begun creating the Cancer Microenvironment. A sort of borderland that is hard to cross. All avenues of attack have been shut down and uncontrollable growth is the consequence. This is a dangerous tumor. Cells that are strong and able to fight, push the immune system back and expand further. If more mutations occur, some of the cancer cells will begin to explore the world and spread into other tissues, creating new “tumor towns”. This is what makes cancer so harmful; it takes up space and steals nutrients, leaving no room for the body to function. If this continues for too long, organs will shut down. However, this tactic is a dead end; the more successful cancer gets, the more damage it does to itself. When the body dies, the cancer dies too. Humanity is determined to win this game, and thousands of scientists are researching new and better ways of killing cancer, such as immunotherapy. This therapy modifies the body’s own immune cells to kill cancer better than any medicine can. It is like giving building inspectors machine guns and flamethrowers. This video was made possible through viewer support and a grant from Gates Ventures.