Prostate cancer is the most common malignancy among men in the United States. It is also the second most common cause of cancer-related deaths. Despite improved treatments for prostate cancer, many patients with advanced disease eventually develop drug resistance. Researchers in the Center of Excellence for Evolutionary Therapy at Moffitt Cancer Center believe that adaptive treatments based on evolutionary principles may be an effective approach to prostate cancer treatment by preventing the development of drug resistance and prolonging patient survival.
In an article published today in Nature Communications, the research team provides a closer look at a model and data showing that individual patient alterations in the prostate-specific antigen (PSA) biomarker early in treatment can predict outcomes to later treatment cycles of adaptive therapy. These models could eventually be used to devise patient specific treatments according to changing tumor growth and biomarker patterns.
Patients with prostate cancer are commonly treated with radiation therapy or surgery followed by androgen deprivation therapy (ADT) at the highest tolerated dose to kill as many cancer cells as possible. While initial responses to this approach are often effective, eventually patients develop drug resistance and their tumors recur.
“Continuous treatment, by maximally selecting for resistant phenotypes and eliminating other competing populations, may actually accelerate the emergence of resistant populations—a well-studied evolutionary phenomenon termed competitive release,” said study author Heiko Enderling, Ph.D., associate member of Moffitt’s Department of Integrated Mathematical Oncology.
Enderling and his team, in collaboration with scientists from Duke University, University of North Carolina and Arizona State University, believe that instead of using a continuous maximum tolerated dose, a better approach would be to use adaptive therapy with intermittent dosing. This treatment strategy is based on changing patterns of