Researchers report results from their study using mathematical modeling to show that cell turnover impacts drug resistance and is an important factor that governs the success of adaptive therapy.
Cancer treatment options have increased substantially over the past few decades; however, many patients eventually develop drug resistance. Physicians strive to overcome resistance by either trying to target cancer cells through an alternative approach or targeting the resistance mechanism itself, but success with these approaches is often limited, as additional resistance mechanisms can arise.
Researchers in Moffitt’s Integrated Mathematical Oncology Department and Center of Excellence for Evolutionary Therapy believe that resistance may partly develop because of the high doses of drugs that are commonly used during treatment. Patients are typically administered a maximum tolerated dose of therapy that kills as many cancer cells as possible with the fewest side effects. However, according to evolutionary theories, this maximum tolerated dose approach could lead to drug resistance because of the existence of drug resistant cells before treatment even begins. Once sensitive cells are killed by anti-cancer therapies, these drug resistant cells are given free rein to divide and multiply. Moffitt researchers believe an alternative treatment strategy called adaptive therapy may be a better approach to kill cancer cells and minimize the development of drug resistance.
«Adaptive therapy aims not to eradicate the tumor, but to control it. Therapy is applied to reduce tumor burden to a tolerable level but is subsequently modulated or withdrawn to maintain a pool of drug-sensitive cancer cells,» said Alexander Anderson, Ph.D., chair of the Integrated Mathematical Oncology Department and founding director of the Center of Excellence for Evolutionary Therapy.
Previous laboratory studies have shown that adaptive therapy can prolong the time to cancer progression for several different tumor types, including ovarian, breast and melanoma. Additionally, a clinical trial in prostate cancer patients at Moffitt has shown that compared to standard treatment, adaptive therapy increased the time to cancer progression by approximately 10 months and reduced the cumulative drug usage by 53%.
Despite these encouraging results, it is unclear which tumor types will respond best to adaptive therapy in the clinic. Recent studies have shown that the success of adaptive therapy is dependent on different factors, including levels of spatial constraint, the fitness of the resistant cell population, the initial number of resistant cells and the mechanisms of resistance. However, it is unclear how the cost of resistance factors into a tumor’s response to adaptive therapy.
Story Source: Materials provided by H. Lee Moffitt Cancer Center & Research Institute. Note: Content may be edited for style and length.