Abstract SY29-01: Targeting DNA repair factor dysfunction in advanced prostate cancer

Abstract

Abstract Prostatic adenocarcinoma (PCa) is the third leading cause of cancer death in U.S. men. Organ-confined PCa can be effectively managed, but there is no durable treatment for advanced disease. Advanced PCa is treated through androgen deprivation therapy, often coupled with direct androgen receptor (AR) antagonists, as PCa is exquisitely dependent on AR activity for cell survival and proliferation. Unfortunately, relapse is common; recurrent disease arises largely due to resurgent AR activity with 2-3 years, and there is no cure for this castration-resistant phase (castration-resistant PCa; CRPC). Thus, there is a significant need to develop new means for targeting recurrent AR activity or to develop adjuvant therapies in advanced PCa. Emerging data from our laboratory and others strongly support the concept that alterations in DNA damage repair (DDR) pathways are more common than previously thought in sporadic PCa, and that alterations in these pathways may afford new, more effective means of therapeutic intervention. New studies to be discussed will address underlying mechanisms of action with regard to the pathway and identify clinically actionable ramifications of DNA repair dysfunction. Major concepts to be considered include 1) new findings implicating differential functions of p53 somatic mutations on PCa behavior and response to therapeutic intervention and 2) differential roles of DNA-dependent protein kinase (DNAPK) in controlling PCa progression. Findings to be discussed strongly support a model wherein selected DDR pathways can be developed as therapeutic targets to tailor treatment for prostate cancer and improve outcome for advanced disease. Citation Format: Karen E. Knudsen. Targeting DNA repair factor dysfunction in advanced prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY29-01. doi:10.1158/1538-7445.AM2017-SY29-01