Why is this important you say (or not...)? Because we are moving towards the use of targeted therapies. Therapies that, for the most part, assume that there are critical *targetable* mutations that all tumour cells share. Sadly this is unlikely to be true for most cancers.
An exception could be CML or Chronic Myeloid Leukemia, a type of tumour in which I started working recently during the IMO workshop (+Artem Kaznatcheev describes it nicely here [link]). Our clinical experts were quite clear that there is no heterogeneity in CML. There is only a key mutation, BCR-ABL, driving CML that if messed with, controls the cancer. That lack of genetic heterogeneity could explain why treatments like imatinib are so effective.
But it does not work every time, it does not work the same for everybody and even if there is not substantial genetic heterogeneity there are other elements that explain intra-tumour heterogeneity. +Chandler Gatenbee and I came with this list, which is certainly not exhaustive, during a brainstorming session:
There are tumour cells with different degrees of stemness, cells at different states of the cell cycle, different proliferative potential, expresion of Beta-catenin...and that is before we even start considering the microenvironment of the tumour (access to oxygen, other cells, that is, non-tumour cells...). Could it be the reason why not all patients respond the same way to the, otherwise very successful imatinib? I think there is a good chance that heterogeneity could be behind that. Let's now see if our clinicians at Moffitt (or maybe elsewhere) can give us a information we could use to correlate CML heterogeneity and response to imatinib.