Unfortunately, metastatic cancers are usually fatal. While many highly effective therapies have been developed over the last few decades, cancer cells have a remarkable capacity to evolve resistance, which allows them to overcome the treatment and begin growing again. My goal is to use our understanding of the principles of evolution to optimize the patient benefit from existing treatments. The basic principle is that cancer cells, like any evolving organism, can only adapt to the “here and now” – they can never anticipate the future. But, we can! That is, our ability to understand and exploit the tumor cell’s evolution is our greatest advantage and so, rather than letting the cancer use evolution to defeat our therapy, we focus on using evolutionary dynamics to increase the efficacy of our treatment. For example, by using small but strategically timed doses of drug, we can apply evolutionary dynamics to indefinitely control even very aggressive cancers in mice with a single chemotherapy agent. The first clinical trial using this “adaptive therapy” strategy is under way in men with metastatic prostate cancer. A second strategy (termed “double bind”) uses an initial treatment to both reduce the cancer population and then follow this with a second treatment that specifically targets the adaptive strategy the cancer cells used to evolve resistance. For example, we have found that some breast cancers evade immunotherapy by proliferating very rapidly – essentially producing new cells faster than the immune system can kill them. However, these adapted cells, because they are proliferating so fast, are highly vulnerable to conventional chemotherapy. Interestingly, when we treat them with chemotherapy, we select for cells that grow slowly and are, thus, vulnerable once again to immunotherapy. This is called an “evolutionarily futile cycle” and, as long as we keep the cancer cells cycling back and forth between these two therapies, the patient remains alive and well. Thus, by applying a sequence of treatment using a strategic approach based on evolutionary principles we find that we can take existing treatments and greatly increase the duration of tumor response using much smaller doses – thus both maximally prolonging survival with a high quality of life.
Don’t kill cancer, learn to live with it, say scientists.