Despina Siolas, MD, PhD

Overview

Aim: Treatment and Therapy

The majority of pancreatic ductal adenocarcinomas (PDACs), the most common type of pancreatic cancer, harbor mutations in the KRAS gene resulting in over-activated KRAS protein. While it has been well appreciated that there are multiple, different mutations in the KRAS gene that can cause over-active KRAS, emerging data indicates that individual KRAS mutations may have distinct characteristics affecting how tumors behave. Specifically, patients with KRASG12R mutations, experience longer survival compared to those with other KRAS mutations although the reasons for this is currently unclear.

Despina Siolas, MD, PhD, Assistant Professor of Medicine from the Weill Medical College of Cornell University, a 2026 Hirshberg Foundation Seed Grant Award recipient is seeking to understand why. Using novel, mutation-specific models of KRAS mutant PDAC, her lab found that KRASG12R mutant tumor microenvironments are biologically distinct from other KRAS mutants, containing more active immune cells. The focus of Dr. Siolas’s Seed Grant project, Genotype-guided immunotherapy for pancreatic cancer, is to uncover the molecular mechanisms downstream of KRASG12R mutations that generate this immune-permissive tumor microenvironment. Based on preliminary data from her group, they will test the hypothesis that specific immunotherapy combinations, those focused on stimulating the antigen presenting cells (APCs) in the tumor microenvironment, will be efficacious in KRASG12R mutant PDAC models. As currently immunotherapeutic approaches have been largely ineffective for pancreatic cancer patients, this work from Dr. Siolas’s lab could identify and define a subset of patients who may benefit from immunotherapy as treatment and identify specific immunotherapeutic strategies that will be most successful in this population.

The Hirshberg Foundation is delighted to support Dr. Siolas’s research with a 2026 Hirshberg Foundation Seed Grant Award. As she wrote to us, “Hirshberg Foundation Seed Grant funding is transformative because it gives investigators the opportunity to pursue promising ideas and generate the critical data needed to take them to the next level. This Hirshberg Foundation Seed Grant will allow us to deepen our understanding of the biology that drives KRAS mutant pancreatic cancer and translate those insights toward new therapeutic strategies. I am incredibly grateful to the Hirshberg Foundation and its supporters for investing in innovative research at such an important stage. Thank you for supporting our work and for everything the Hirshberg Foundation does for the pancreatic cancer community. I am very excited to get started.”