Assistant Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine
University of Cincinnati
Targeting the Lipid-Mobilizing Enzyme PLAAT3 to Overcome Metabolic and Acquired pan-RAS Inhibitor Resistance in PDAC
Overview
Aim: Tumor Biology
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, is characterized by its ability to adapt and become resistant to standard therapies. This ability to adapt and acquire resistance to therapy is a potential threat to the early clinical promise of pan-RAS inhibitors. Understanding the mechanisms that allow tumor cells to adapt will generate new therapeutic strategies that inhibit adaptation while also killing tumor cells. One way that PDAC tumor cells adapt to treatment is by changing how they make energy (a molecule called ATP) which is a process termed metabolic adaptation.
Nina Steele, PhD, an Assistant Professor of Gastroenterology and Hepatology at the University of Cincinnati, and a Hirshberg Foundation Seed Grant recipient has found that a protein called PLAAT3 is a regulator of the metabolic adaptations that are required for tumor cells to acquire resistance to drug treatments. PLAAT3 is highly expressed in PDAC tumor cells compared to healthy cells and when PLAAT3 protein was removed from tumor cells it resulted in reduced cell growth and death. Dr. Steele’s Seed Grant project Targeting the Lipid-Mobilizing Enzyme PLAAT3 to Overcome Metabolic and Acquired pan-RAS Inhibitor Resistance in PDAC will evaluate if PDAC tumor cells require PLAAT3 activity for survival and explain how PLAAT3 contributes to acquired resistance to pan-RAS inhibition. Dr. Steele’s project would provide evidence establishing PLAAT3 protein as a key regulator of metabolic adaptation in acquired drug resistance by PDAC tumor cells and provide a path forward to overcome therapy resistance in pancreatic cancer patients.
The Hirshberg Foundation is proud to support Dr. Steele’s 2026 Hirshberg Foundation Seed Grant Award to uncover the mechanisms of drug resistance leading to new treatment strategies.
Dr. Steele wrote to us to say, “I am honored and thrilled to be awarded this prestigious grant! This is truly a significant impact for a small lab, and an Early Stage Investigator, like myself, during a particularly challenging funding climate. I would like to express my deepest appreciation for the work of the Foundation and the support it has provided for pancreatic cancer research over the years.”
