Cancer development involves accumulating mutations, requiring specific genetic alterations in sequence to enable abnormal proliferation, DNA damage tolerance, survival, and evasion of immune detection.

“The combination lock is just spinning, spinning. The combination has to be dialed in the right sequence, just like when you're opening your gym locker or you don't get cancer. You've got to get your tumor suppressor early and in the right order before your activated oncogene comes along. You're randomly spinning the lock. You're picking up lots of past true mutations, not just true drivers. So these incidental mutations that happen here and there. So as that's happening, you finally click important components of the program. But along the way, some of those are actually mutations that are seen as foreign by the immune system. And if they're too visible, far out there, if they're too far out there, then they're gone. So it has to be the right kind of genetic alteration that will give the cell what it needs to be able to proliferate abnormally, to be able to sustain a lot of DNA damage as it accumulates and not commit suicide as a consequence. be able to handle all the other adverse features and filters of the tumor microenvironment that you enumerated.”