GrouseMan wrote:Well said Catstaff! I would go on to say that almost always the mix of mutations in a Met is different than it was in a primary. That's why its important to get biopsies of Mets if possible to help direct chemotherapy or Immunotherapies. Your primary could have been removed and gene tested, but that doesn't mean your Met's have the same set of mutations in its genes it could have a subset or new set of mutated genes. This is one of the main reasons we have such a difficult time treating advanced solid tumor cancers of any kind. A particular Met might be composed of many different mutated cancer cells even. A biopsy and tests on different parts of the met might yield different results. Outer parts of the tumor with a good blood supply might have one set where deep inside where it might not be as well vascularized could have another set.
This is why a lot of oncologists don't put a lot of faith in Genetic testing up front. Usually they have only the primary to test and its not a reliable indication of what the Met might be like. They stick pretty much with tried and true (ie Clinical trials) methods that appear to work for however long for a particular type of cancer. Everyone's Colon cancer is unique to that individual. They are as unique as each of us are to one another.
In preclinical testing of cancer chemotherapies and immunotherapies we use a lot of mouse models. They are at best crude approximations of a patient. They are often referred to as Xenographes. We might find a drug that works phenomenally in these models but only moderately well once in the clinic. I was involved in the discovery and development of one such drug. It was actually the first drug that our tumor biologists had ever seen where the mouse was cured and lived out its life to old age. That had never been seen in these Xenograph tests before. What is done is a tumor of a certain size is implanted in usually am immune compromised mouse species. These tumors are standard tumor types (ATCC Colon Types are Colo205, HCT-2998, HCT-116, HCT-15, HT29, KM12, and SW-620 all of human origin). The tumor is grown to a certain size for several days. Then treatment begins in the treated leg and usually drug vehicle is used on the control. Sort of matched pairs you might say. The size of the tumors are observed over several weeks and you end up with two curves, one showing growth in the controls verses the treated leg. Mind you this is done with many sets of mice at different doses and schedules to find the optimal one. In the tests of this particular drug - the optimal set of dose and schedule the test mice survived and tumors completely disappeared at least in terms of being able to find or locate them including biopsy! At that point dosing was stopped and they waited for the tumors to start to grow back. In the case of standard treatment methods using standard approved chemo drugs these tumors always came back. In the case of this particular drug treatment they never did. The treated mice lived out their natural lifespan. We thought we had a winner!
So what am I getting at. Well We went into human trials and this drug although useful and it had gotten approval, it didn't work nearly as well as we had hoped in people. The tumors in people mutated to become resistant to the drug over time. It was a much more complex situation than the mouse models suggested. Since then Anti-Cancer drug developers have learned a great deal more. And we constantly apply whats learned. We go after the mutated gene itself now rather than the one than the normal gene that controlled the proliferation of the tumor to begin with. So we now have 3rd generations of these drugs that do a better targeted job, but in people the tumor still finds a way to resist in some folks.
Unlike Bacterial, Viral and other diseases in cancer even for a particular cancer type we are attempting to treat thousands of really different tumors unique to each person.
GrouseMan (Former Anti-cancer drug discovery chemist).