in The Ohio Union

Castration resistance in prostate cancer arises through both natural selection and phenotypic plasticity

Thursday, July 20 at 6:00pm

SMB2023 SMB2023 Follow Thursday during the "PS02" time block.
Room assignment: in The Ohio Union.
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Nadia Wright

Arizona State University
"Castration resistance in prostate cancer arises through both natural selection and phenotypic plasticity"
Recurrent prostate tumors are commonly treated with a total androgen blockade via chemical castration. In turn, cancerous cells have been known to respond with an evolutionary up-regulation of androgen receptors (AR), thus prolonging cell proliferation and delaying apoptosis. Prostate epithelial cancers treated with androgen ablation therapy invariably become castration resistant. However, the primary mechanism remains unknown. Suggested hypotheses include phenotypic plasticity and natural selection. Here we show that castration resistance in prostate cancers treated with androgen ablation arises through natural selection acting on phenotypic plasticity. We found that tumor aggressiveness, measured as growth rate of serum concentration of prostate specific antigen (PSA), correlates positively with the number of treatment cycles. Additionally, we found a signal of increasing tumor aggressiveness with cycle in both on and off-treatment phases. This result argues against the plasticity hypothesis and is consistent with evolution by natural selection. If plasticity were the mechanism, then tumor aggressiveness would not correlate with cycle. This result can help inform clinical management of prostate cancer treated with androgen ablation. Identification of the exact evolutionary mechanism will almost certainly yield insight into more efficacious treatment schedules, and drug combinations, while maintaining patient quality of life and delaying the onset of castration resistance.
Additional authors: Jonathan Trautman, Department of Biological Sciences, Northern Arizona University; Khoa Dang Ho, School of Life Sciences, Arizona State University; John D. Nagy, School of Mathematical and Statistical Sciences, Arizona State University

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Annual Meeting for the Society for Mathematical Biology, 2023.