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Mathematical Biology Seminar

March 1, 2023 - 10:30am

Speaker: Dr. Renee Brady-Nicholls, Moffitt Cancer Center
Title: Improving Prostate Cancer Treatment Using Range-Bounded Adaptive Therapy
Abstract: Prostate cancer remains the most prevalent cancer in men in the US. While continuous first-line hormone treatment at maximum tolerable dose is the standard of care, continuous treatment often selects for the resistant phenotypes resulting in castration resistant disease. Second-line hormone therapy options, such as abiraterone acetate (AA), have been proven effective for metastatic castration resistant prostate cancer (mCRPC). Adaptive AA, whereby treatment is cycled on and off using patient-specific treatment triggers, has been shown to be effective at reducing toxicity and prolonging time to progression. It is hypothesized that cycling through treatment allows sensitive cells to competitively suppress resistant cells, thereby increasing the amount of time that treatment is effective. It has been proposed that there exists a subset of patients for whom this competition can be enhanced through modifications to adaptive AA. Here, we investigate this by calibrating a simple mathematical model to longitudinal prostate-specific antigen data from 16 mCRPC patients undergoing adaptive AA. Model parameters are then used to simulate range-bounded adaptive therapy (RBAT) whereby treatment is modulated to maintain PSA levels between pre-determined patient-specific bounds. Model simulations of RBAT are compared to the clinically applied adaptive therapy and show that RBAT can further extend time to progression, while reducing the cumulative dose patients receive. This is a promising next step in improving patient care, particularly in those patients who do not respond well to conventional adaptive therapy.