Cancer chemotherapy precision medicine. Calculated treatment. Part 1. 12
Current sequential chemotherapy in “lines of treatment” is ineffective and outdated. Leading cancer genetics expert discusses new approach to choose chemotherapy for cancer patients. It is called “calculated treatment”. Precision medicine cancer treatment requires better selection of chemotherapy. Mathematical modeling selects best combination of chemotherapy to treat cancer patient. Results have been tested in colon cancer, melanoma and pancreatic cancer. Dr. Anton Titov, MD. You have published a fascinating editorial in a major medical and scientific journal Nature. It is about an article that described the mathematical modeling of chemotherapy selection for cancer treatment. You called this mathematical approach to chemotherapy selection “a calculated treatment”. Let me quote from your article: “Current common practice for treating cancers is to administer the medications sequentially, starting with the first-line medication and then switching to second line therapy if the tumor relapses. Article authors assess the effectiveness of this approach using mathematical techniques and data from patients with melanoma [skin cancer], with pancreatic cancer and with colorectal cancers. They convincingly demonstrate that sequential treatment strategy PRECLUDES any chance for cancer cure even in the best-case scenario, in which no single mutants confer resistance to two chemotherapy medications. However, authors show that simultaneously combining two or more chemotherapy medications can bring much needed hope for cure to patients.” This is a very important emerging change of strategy of cancer treatment. Dr. Anton Titov, MD. We had already discussed recently this paradigm shift in the structure of chemotherapy selection with Dr. Heinz-Josef Lenz, another prominent colorectal cancer expert. Please tell us more about this “calculated strategy” of cancer treatment and chemotherapy selection, including treatment of colon cancer or melanoma. There was a brilliant collaboration between Martin Nowak… Dr. Nowak is a computational biologist currently at Harvard Medical School. He got together with Dr. Bert Vogelstein, who’s one of the leading cancer geneticists in the world. And they began to look at this issue – How could we improve prediction of chemotherapy efficacy in cancer patients. The idea was that there are a lot of chemotherapy medications that can reduce tumor size. But almost always the tumor develops resistance to chemotherapy and then it re-emerges again. A molecular escape of the tumor. Dr. C. Richard Boland, MD. Yes, a molecular escape. Maybe 1 cell in 10,000 cancer cells in the primary tumor is a [medication-resistant] mutant, but if chemotherapy kills off all the competition, and this cell is not affected by chemotherapy, then a resistant clone of cells will emerge and treatment will not work anymore. We have all seen that molecular escape of the tumor happen so many times. It’s a tragic event, when a person gets an initial response to chemotherapy, hopes that this cancer remission will be durable. But then tumor develops resistance and we have to try another medication. Dr. C. Richard Boland, MD. You might say: “Why not use several chemotherapy medications at the very beginning?”. You cannot do that, because medication toxicity increases too. So there are some natural limits to how you can combine all these chemotherapy medications. And also the feeling was – if there are many different mutations in cancer tumor, then you might have to use 3 or 4 or 5 chemotherapy medications. And that will increase the likelihood of toxicity even more.
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