The current hypothesis is that it is similar to bacterial antibiotic escape. Effectively the cells are growing rapidly and acquire mutations. This is why you want to treat with combination chemotherapy. However, there are some big issues. First, we only test drugs in isolation and then sometimes they will try two together after a long long time. This is how leukemia achieved high remission rates back back in the wild wild west days. Today there is a focus on targeted chemotherapies and then of course the holy grail of immunotherapy. I hope we figure out how to program the immune system to great effect. That and viral targeting therapies that use crisper. But these are early days and progress cannot come fast enough.