AUM-302, a novel triple PIM/PI3K/mTOR inhibitor, synergizes with RAS inhibition and impedes the growth of pancreatic ductal adenocarcinoma spheroids and organoids.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a significant contributor to cancer-related deaths in the United States. The limited number of well-defined, druggable targets in PDAC has hindered the development of effective treatments. The PIM/PI3K/mTOR pathways, which regulate cell growth, apoptosis, metabolism, and protein synthesis, are often dysregulated in PDAC, leading to various transformed phenotypes, including unchecked cell proliferation. Here, we demonstrate that the triple kinase inhibitor AUM-302 exhibits strong inhibitory efficacy against PDAC growth in 3D formats, including spheroids and organoids. Experiments were conducted using BxPC-3, Capan-2, MIA PaCa-2, and PANC-1 human PDAC cell lines, hF37 2D organoid-derived PDAC cell line, and primary (hF37, hF31, hF44, hT1) and metast

SUBMITTER: Wen E 

PROVIDER: S-EPMC12932507 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature