Abstract 321: Metformin enhances the efficacy of enzalutamide treatment in castration-resistant prostate cancer

Abstract

Abstract Prostate cancer remains to be the most commonly diagnosed cancer among men in the United states with approximately 268,500 new cases a year. One of the first treatment options for men with prostate cancer is androgen deprivation therapy (ADT), however, recurrence and metastases after ADT remain an issue and are categorized as castration-resistant prostate cancer (CRPC). Enzalutamide, an FDA approved drug currently prescribed to patients with CRPC, inhibits androgen receptor (AR) nuclear translocation preventing the transcriptional activity of AR. This therapy typically only extends the survival of patients with CRPC and can lead to Enzalutamide-resistance over time accenting the importance of new therapy targets. Metformin, a commonly used FDA approved therapy for type 2 diabetes, has been recently investigated as potentially having anti-tumor effects in many cancer types. In this study, we use Enzalutamide and Metformin in combination to explore possible re-sensitization of Enzalutamide-resistant CRPC to Enzalutamide. Recently, we have tested the effects of this combination treatment on cell viability, drug synergy, and cell proliferation in Enzalutamide-resistant CRPC. After treatment, we see a decrease in cell proliferation and viability as well as a synergistic effect of both Enzalutamide and Metformin in Enzalutamide-resistant CRPC. Following these results, we sought to explore how this combination treatment effected key signaling markers for EMT, WNT signaling, and TGFβ signaling as well as key signaling markers for prostate cancer such as AR and prostate specific antigen (PSA). Since Metformin inhibits Complex I of oxidative phosphorylation, we also tested this combinational treatment using seahorse analysis to determine the mitochondrial respiration. After initial testing, we will continue to move forward in testing the effects of this combination treatment in Enzalutamide-resistant CRPC as well as further elucidate the underlying mechanisms contributing to this phenotype. Citation Format: Kendall Elizabeth Simpson, ZhuangZhuang Zhang, Qiongsi Zhang, Xiaoqi Liu. Metformin enhances the efficacy of enzalutamide treatment in castration-resistant prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 321.