Dr Townsend on the Genetic Evolutionary Trajectory of Prostate Cancer

Jeffrey P. Townsend, PhD, Elihu Professor of Biostatistics and Professor of Ecology and Evolutionary Biology, co-leader, Genomics, Genetics, & Epigenetics Research Program, Yale School of Public Health, elucidates a novel approach to comprehending the genetic evolutionary trajectory of prostate cancer at different stages of the disease.

Research presented at the 2024 AACR Annual Meeting delved into the effects of prostate cancer driver mutations and how the magnitude of these effects vary by stage. Findings presented during the meeting showed that reveals that low-risk, higher-risk, and metastatic prostate tumors exhibit dynamically varied rates along the trajectory of the disease.

Although the common belief is that low-risk prostate cancer follows a different trajectory compared with high-risk prostate cancer, both disease types can lead to metastases; patients with high-risk disease are simply more likely to progress to metastatic disease, Townsend says. To further identify driver mutations at each level of disease, Townsend and colleagues examined tissue from low-risk prostate cancer, high-risk prostate cancer, and metastatic prostate cancer, as well as normal prostate tissue.

By examining which genes are selected in low-risk and high-risk prostate cancer that lead to metastatic disease can help define the trajectory of the disease, Townsend expands. Additionally, identifying these genes could allow for the development of more effective targeted agents for patients at different stages of prostate cancer, he says.

Townsend also explains that the research involved looking at how different genes interact with each other and this effect on epistasis—how selection is increased or decreased based on this interaction. By better understanding how a specific mutation affects the likelihood of other mutations, it is easier the characterize where a specific patient’s prostate cancer falls on the evolutionary trajectory of the disease, he says, such as which mutations may be the likely next step.

In characterizing the molecular and genetic progress of prostate cancer, future generations of therapy could be based on the anticipation of forthcoming mutations, allowing for potential treatments to prevent patients from experiencing disease progression, rather than initiating treatment when progression occurs, Townsend concludes.