Kirsten Bryant, PhD, Assistant Professor of Pharmacology, has been awarded a $100,000 Seed Grant from the Hirshberg Foundation for her project that seeks to define and target metabolic changes associated with RAS inhibition in pancreatic ductal adenocarcinoma (PDAC).
Intrinsic and acquired resistance to direct RAS inhibition is a critical barrier that must be overcome to advance RAS inhibitor-based therapies for the treatment of PDAC. Bryant hypothesizes that dysregulation of core metabolic pathways contributes to RASi resistance. This Hirshberg Foundation Seed Grant will provide Bryant and her team with crucial funds to expand their analyses of the metabolic function in RAS inhibitor-resistant PDAC to mitochondrial function.
Bryant proposes two approaches for her project. The first will be to assess the efficacy of ONC201, an FDA-approved molecule that selectively activates ClpP and causes mitochondrial dysfunction in RAS inhibitor-resistant PDAC. Additionally, in collaboration with the UNC Metabolomics and Proteomics core, Bryant’s team will perform targeted and untargeted metabolomics to evaluate alterations in primary metabolic pathway in RAS inhibitor-resistant PDAC. Their ultimate goal is to identify novel, targetable vulnerabilities to improve the efficacy of RAS inhibitors for the treatment of pancreatic cancer.
—Tyler Rice, UNC Lineberger Pancreatic Cancer Center of Excellence