AUM-302, a Novel Triple PIM/PI3K/mTOR Inhibitor, Offers Promising Potential in Reducing the Growth of Pancreatic Ductal Adenocarcinoma Spheroids and Organoids

Overview

Renaissance School of Medicine at Stony Brook University Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 13% 5 -year relative survival rate. The limited number of well-defined, druggable targets in PDAC has hindered the development of effective treatments. The PIM/PI3K/mTOR pathways, wh ich regulate cell growth, apoptosis, and metabolism, are often dysregulated in PDAC, leading to various transformed phenotypes. AUM -302, a novel triple PIM/PI3K/mTOR inhibitor, stands out for its unique mechanisms of action. It inhibits PDAC growth by dire ctly binding to the ATP binding site of the PIM kinases and indirectly impacting the PI3K/mTOR pathways. It was hypothesized that AUM-302 has potent inhibitory effects in 3D culture. This study evaluated the efficacy of AUM - 302 in human PDAC cell lines and organoids grown in 2D culture under 3D ultra-low attachment (ULA) conditions and in 3D Matrigel format. Control compounds TP -3654, GDC-0941, and BEZ- 235 that primarily inhibit one/two of the 3 cell signaling pathways, respectively, and DMSO, were used. The half-maximal inhibitory concentrations (IC50) of the test compounds were evaluated using a 3D CellTiter -Glo luciferase assay. The cells were imaged 24, 48, and 72 hours after treatment. In PDAC cell lines and organoids, AUM-302 induced more cell death and inhibited cell proliferation in a dose-dependent manner compared to the control compounds, as evidenced by the change in morphology of the cells and low IC50 values. Overall, AUM-302 shows substantial inhibitory activity towards PDAC cell lines and organ oids. Additional studies in conditions that recapitulate the human tumor microenvironment are needed to confirm AUM-302’s effects.

Competition history

• JSHS 2025 Category not listed

Resources

• National JSHS abstract book ↗

Related projects

Closest projects by meaning, across every fair and year in the corpus.