Abstract A014: Repurposing <i>aprocitentan</i> , an anti-hypertensive drug, as a potential anticancer agent: Targeting endothelin receptors in pancreatic and breast cancer models

Abstract Repurposing Aprocitentan, an Anti-Hypertensive Drug, as a Potential Anticancer Agent: Targeting Endothelin Receptors in Pancreatic and Breast Cancer Models Cancer remains a leading cause of global mortality, with pancreatic and breast cancers representing two of the most aggressive forms, often associated with poor prognosis and limited therapeutic options. Drug repurposing provides a cost-effective and time-efficient strategy to identify novel cancer therapies from existing drugs with established safety profiles. The endothelin system, comprising endothelin-1 (ET-1) and its receptors (ETA and ETB), plays a critical role in tumor progression through promoting proliferation, angiogenesis, and resistance to apoptosis. This study proposes to repurpose Aprocitentan, a dual ETA/ETB antagonist currently approved for hypertension, as a potential anticancer agent. The research will employ in vitro models of pancreatic (MiaPaCa-2, BxPC-3) and breast (MCF-7, MDA-MB-231) cancer cell lines, assessing Aprocitentan’s impact on cell proliferation, apoptosis induction, and angiogenesis-related pathways. Additionally, the interplay between Aprocitentan and the PI3K signaling cascade will be explored using the PI3K inhibitor LY294002. Key molecular and functional assays—including MTT viability assays, Western blotting, ELISA, and PCR—will be utilized to validate mechanistic insights. We hypothesize that Aprocitentan will inhibit cancer cell growth, promote apoptosis, and suppress angiogenic signaling, thereby demonstrating its potential as a repurposed anticancer drug. The outcomes of this study are expected to provide preclinical evidence supporting a novel therapeutic strategy, expanding the application of Aprocitentan beyond cardiovascular disease toward oncology. Citation Format: Rahaf Adnan. Al-Zeer. Repurposing aprocitentan, an anti-hypertensive drug, as a potential anticancer agent: Targeting endothelin receptors in pancreatic and breast cancer models [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Cancer Evolution: The Dynamics of Progression and Persistence; 2025 Dec 4-6; Albuquerque, NM. Philadelphia (PA): AACR; Cancer Res 2025;85(23_Suppl):Abstract nr A014.