Abstract 1699: Targeting mercapturic acid pathway transporter in chemoradiotherapy resistant ovarian cancer

Abstract

Abstract Ovarian cancer is the most common and the most lethal malignancies arising in the female reproductive system. Morbidity and mortality associated with ovarian cancer will continue to impact the female population. Although cisplatin centered chemotherapy is the first line anticancer agent for human ovarian cancer, chemoresistance and adverse side effects remain major hurdles to successful treatment. The effective targets for cancer therapy must be desirably expressed differentially in particular cancers as compared with normal cells. Also, there should be an essential dependence of cancer cells on the target compared to non malignant cells. Ideally, the target should be understood in the context of existing biochemical and signaling frameworks known to play a direct role in a particular carcinogenesis or in regulating the response to therapy. In the context of striking chemo radiotherapy resistance of ovarian cancer and the fundamental role of RLIP as an important mercapturic acid pathway transporter that is essential for survival and therapy resistance in cancers, we investigated the role of RLIP in regulating the critical signaling proteins involved in relaying the inputs from multiple upstream survival pathways and mechanisms contributing to chemo radiotherapy resistance in ovarian cancer. Compounds that inhibit, deplete, or downregulate RLIP will function as wide spectrum agents to treat ovarian cancer, independent of common signaling pathway mutations. Here, we demonstrate that RLIP expression is significantly greater in ovarian cancer cells than in non malignant cells, and RLIP is an essential requirement for cancer formation, and its depletion or inhibition will prevent ovarian carcinogenesis as well as metastases. Taken together, the results of our studies provided insights into a novel anticancer effect of RLIP depletion/inhibition on ovarian cancer and might open new therapeutic avenues for the treatment of ovarian cancer. Supported in part by the Department of Defense grant W81XWH 22 1 0331. Funding from the Beckman Research Institute of City of Hope is also acknowledged. Citation Format: Sharad S. Singhal, Er Yue, Prakash Kulkarni, David Horne, Sanjay Awasthi, Edward Wang, Ravi Salgia. Targeting mercapturic acid pathway transporter in chemoradiotherapy resistant ovarian 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 1699.