Cancer chemotherapy precision medicine. Calculated treatment. Part 2. 13
How to select chemotherapy for a patient? What is the best combination of medications to cure cancer? This is called “calculated treatment”. It is chemotherapy cancer treatment selection for precision medicine era. Leading cancer genetics expert discusses personalized medicine methods to treat cancer. Dr. C. Richard Boland, MD. So this is what the mathematicians did together with biologists: The biologists figured out the proliferative fraction a tumor. And it’s something like 13%. So if you have 100 cells today then in 24 hours you might have a 113 cells. But the replication of cancer cells is sloppy, they often have some genetic instability. So some proportion of cancer cells do not survive. Also there is typically an immune response trying to kill off cancer cells. So tumor has a death rate too. The difference between the tumor’s proliferation rate and its death rate is what accounts for cancer growth. But these two numbers are pretty close. A typical cancer tumor proliferation rate was 13% but the tumor death rate was 11%. So there’s just a 2% difference between proliferation rate and growth rate. But a 2% difference over time is what will make cancer grow. So when you treat cancer with chemotherapy medication, you either decrease tumor’s proliferation rate or you increase tumor’s death rate. When those two numbers cross, and when the tumor’s death rate is higher than tumor’s growth rate, then tumor will shrink and recede. So they did mathematical modeling of tumor growth. They can take all the variables that the biologists can give to mathematicians. Variables are: tumor growth rate, tumor death rate, tumor mutation rate, and the likelihood of any given mutation causing the tumor to develop resistance to chemotherapy. And also what was the impact of chemotherapy being used. Most of the chemotherapy medications are usually given to patients in sequential manner. Dr. C. Richard Boland, MD. But if you gave chemotherapy medications together at the same time – [scientists were able to model tumor growth rate, its death rate, and mutation rate] just two medications were theoretically enough to keep the tumor from coming back. This was true as long as there was not a single mutation in a cancer cell that would simultaneously provide resistance to both of those chemotherapy medications. This is what these results mean. Doctors and biologists can give mathematicians real numbers about cancer tumor growth rates and resistance-conferring mutations. And mathematical modeling can hopefully come up with the least toxic combination of chemotherapeutic medications that will be enough to prevent the cancer from recurring. So that tumor does not have “molecular escape” due to a mutation that gives resistance to the cancer chemotherapy. As we move forward, it’s not going to be just empirical cancer therapy. We will be able to use mathematical calculations to get our therapy more precise, safe and effective. So this is a very novel and exciting idea – to move from sequential lines of therapy to a calculated strategy of selecting simultaneous chemotherapy regiments. Of course, we have to keep in mind potential toxicity. Dr. Anton Titov, MD. But it’s a very exciting line of research! – I agree!
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