Eventos

Speaker: Christopher J. Halbrook, PhD – Assistant Professor, Molecular Biology and Biochemistry. School of Biological Sciences – University of California, Irvine. Irvine, USA.

Abstract:

Pancreatic ductal adenocarcinoma (PDA) remains one of the deadliest major cancers. A key barrier to PDA treatment is the physiology of the tumors, characterized by a densely fibrotic extracellular matrix deposited by fibroblasts, rich with immune cell infiltration. The diversity of epithelial, stromal, and immune cell populations within pancreatic tumors provides numerous avenues supporting cancer growth and survival. Our work has shown that disruption of metabolic crosstalk between different tumor compartments functions to impair tumor growth, reduce immune suppression, and potentiate response to chemotherapy.
Recently, we have identified an axis of crosstalk between clonal populations of cancer cells driven by a differential integrated stress response. Targeting the resulting nutrient exchange by degrading exogenous asparagine sensitizes pancreatic tumors to mitochondrial inhibition. Our current efforts aim to characterize how this treatment remodels PDA tumors in both primary and metastatic disease models and determine the pre-clinical utility of this approach. While these seminal studies only begin to describe the metabolic interactions shaping the microenvironment, they demonstrate the potential of uncoupling metabolic symbiosis to target pancreatic cancer.