Abstract 1522: High-throughput screening identifies HSP-90 inhibitor for pancreatic cancer therapy

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Currently, it has an overall five-year survival rate of about 13%. This poor prognosis is attributed to the disease's late-stage diagnosis, rapid progression, and high resistance to available therapies. PDAC tumors often exhibit metabolic plasticity and oncogenic signaling dependencies, contributing to their ability to evade treatment, sustain growth under adverse conditions, and develop resistance to the current standard of care. These characteristics highlight the urgent need to identify novel therapeutic targets. In our study, a high-throughput drug screening was conducted to identify novel compounds capable of targeting key survival mechanisms and metabolic pathways in PDAC cells. Among the tested compounds, PU-H71, a heat shock protein 90 (HSP90) inhibitor, emerged as a promising candidate. Functional assays revealed that PU-H71 effectively inhibits the growth and proliferation in a panel of PDAC cell lines. Pathway analysis revealed that PU-H71 acts by disrupting multiple metabolic pathways. Our findings identify PU-H71 as a potent therapeutic candidate for PDAC treatment. Citation Format: Chiamaka Joy Ezeh, Darren Binder, Rohan Binder, Zeribe C. Nwosu. High-throughput screening identifies HSP-90 inhibitor for pancreatic cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1522.