Personalized cancer treatments have greatly improved the lives of patients; however, many eventually develop resistance to these targeted drugs. Instead of simply using another targeted agent against a resistant tumor at a maximum tolerated dose, Moffitt Cancer Center researchers are approaching the problem of resistance from a different direction -; evolutionary science. In a new article published online ahead of print in Cancer Research, members of Moffitt's Center of Excellence for Evolutionary Therapy present a case study of an adaptive treatment approach based on evolutionary principles in prostate cancer and suggest that these strategies may provide a path toward improved multidrug adaptive therapies.
Patients with progressive prostate cancer are often treated continuously or intermittently with drugs that deprive their tumors of androgen. These drugs can work well initially, but eventually resistance develops and tumors regrow. Results from several clinical trials at Moffitt have revealed that adaptive therapy in prostate cancer patients is a promising alternative approach. In adaptive therapy, patient treatment is altered, stopped or reinitiated based on how the tumor responds to treatment.
The goal of adaptive therapy is to maintain a controllable stable tumor burden by allowing a significant population of treatment sensitive cells to survive. According to evolutionary principles, these remaining easy-to-treat sensitive cells block the growth of the resistant tumor cell populations that are difficult to treat. In this approach, it is possible that the tumor may never be completely eradicated; rather, the tumor may remain relatively stable, thereby limiting the development of uncontrollable drug resistance." Alexander Anderson, Ph.D., chair of Moffitt's Department of Integrated Mathematical Oncology and director of the Center of Excellence for Evolutionary Therapy
Despite the promise of this strategy for prostate cancer, there are several challenges that physicians will need to address when designing the optimum adaptive treatment approach. This is particularly true for approaches that use multiple drugs, as it is unclear if the drugs should be given simultaneously or sequentially, or how often or how long breaks from drug treatments should be used. "Until now, there has not been a clear strategy to extend adaptive therapy to include additional treatments," said Jeffrey West, Ph.D., a Moffitt postdoctoral student and mathematician behind the research. Related Stories
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