Followers of this blog (or even just casual readers) know that heterogeneity is a key aspect of cancer. Not that I am saying that this is my idea, far from it. Many people have championed it in the last few years including my colleague +Alexander Anderson. A couple of years ago CRUK’s Charles Swanton and his team produced convincing clinical evidence of the existence of phenotypic heterogeneity in kidney cancer [news,article] and a lot more people started paying attention. Since then researchers have found evidence of heterogeneity in other types of cancer such as prostate, bone or Barrett’s esophagus.
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: