According to the American Cancer Society, prostate cancer is the second-leading cause of cancer death in American men. Development of treatments can be challenging due to the resistance of prostate cancer cells to conventional androgen-deprivation therapy.

Recently, the FDA has approved several new treatment options for castration-resistant prostate cancer patients, or CRPC, such as Olaparib. These treatments, however, have limitations that leave out a majority of prostate cancer patients.

“The treatment requires patients to carry mutations in their DNA repair genes, but more than 70% of patients do not carry these genes,” said Chunhong Yan, PhD, a professor of biochemistry and molecular biology at the Georgia Cancer Center and Medical College of Georgia at Augusta University.

The mutations that are needed for these treatments to work are in the homologous recombination repair, or HRR, genes. Fewer than 30% of CRPC patients carry these genetic alterations, meaning other patients are unable to take advantage of the treatment.

Yan’s latest research, titled “Mitochondrial Uncoupling for Prostate Cancer Therapy,” aims to fill that gap in treatment.

“The objective of this application is to address this limitation and explore an innovative strategy that repositions FDA-approved drugs to sensitize HRR-intact prostate cancer to prostate cancer cells to polymerase-based therapies,” he said.

Yan and his team plan to do this by investigating how these drugs target mitochondrial events to induce the vulnerability of prostate cancer cells to polymerase inhibitors, also known as PARP inhibitors. PARP inhibitors are a type of targeted cancer drug that can induce DNA damage that requires HRR genes to repair. They are used in cancer treatments by blocking poly (ADP-ribose) polymerase enzyme [AM1] used in DNA repair, which can cause cancer cells to die. During this investigation period, they will determine the efficacy of an FDA-approved drug in sensitizing CRPC to PARP inhibitors.

“Currently, we are using this period to gather data, particularly to assess the safety profile of this new therapy using genetic mouse models,” said Yan when asked about the timeline of this project. He hopes that within the next three to four years, they will have enough data to create a clinical trial that can be used on patients.

While his focus is currently on prostate cancer, Yan said that it is possible to expand this work into other cancers, such as ovarian and breast cancer, to develop new treatments.

“Work like this is very expensive, and we could not even start it without the funding that Paceline provided us,” he said.

Since 2019, Paceline has raised almost $1.7 million for innovative cancer research and has funded over 30 researchers and their projects at the Georgia Cancer Center.

This year, Paceline is expanding its signature fundraising event, PaceDay, to make supporting cancer research more accessible to all by including a walk and run option in addition to the bike riding option. PaceDay 2025 is scheduled for Oct. 5, and you can sign up by visiting the website.