Targeting PRX4 to sensitize prostate cancer to radiation (Radiation Medicine and Markey Cancer Center Collaborative Bench to Bedside pilot)

"The exploration of radioresistance in the context of prostate cancer (PCa) treatment is of paramount significance, reflecting a critical gap in our understanding that directly impacts clinical outcomes and patient wellbeing. PCa remains a significant public health concern, and radiotherapy is a cornerstone in the management, yet the emergence of radioresistance presents a formidable obstacle to achieving optimal therapeutic responses. Unraveling the molecular intricacies that underlie radioresistance in PCa is imperative for the development of
targeted interventions that can enhance treatment efficacy. The peroxiredoxin (PRX) family of proteins functions as cellular antioxidants that mediate oxidative signaling in physiological conditions as well as scavenge reactive oxygen species (ROS) to promote cell survival under oxidative stress. Our preliminary data demonstrate that
aberrantly high level of PRX4 is commonly found in specimens of patients, murine models as well as PCa cell lines. In addition to driving prostate cancer cell movement and invasion, we also found that depletion of PRX4 sensitized PCa cells to ionizing radiation both in culture as well as in mouse xenograft model. We hypothesized that PRX4 functions as a shield of radiation to spare prostate cancer stem cells (PCSCs), and targeted disruption of PRX4 sensitizes prostate cancer to radiation. The objective of this study is to elucidate the mechanism by which PRX4 contributes to radioresistance and to evaluate the efficacy of targeting PRX4 as neoadjuvant chemotherapy for radiation treatment using cell culture and preclinical mouse models."