Exploiting pancreatic cancer metabolism: challenges and opportunities

• DOI: 10.1016/j.molmed.2024.03.008
• Publication Date: 2024-04-10T12:12:06Z
• Authors: Maria Chiara De S...; Bruno Bockorny; Emilio Hirsch; Paola Cappello; Miriam Martini
• Keywords: Pancreatic Neoplasms; Glutamine; heterogeneity; immunotherapy; metabolic reprogramming; mitochondrial metabolism; pancreatic cancer; tumor microenvironment; Tumor Microenvironment; Autophagy; Humans; Animals; Energy Metabolism; Amino Acids, Branched-Chain; Carcinoma, Pancreatic Ductal; Mitochondria

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer, known for its challenging diagnosis and limited treatment options. The focus on metabolic reprogramming as a key factor in tumor initiation, progression, and therapy resistance has gained prominence. In this review we focus on the impact of metabolic changes on the interplay among stromal, immune, and tumor cells, as glutamine and branched-chain amino acids (BCAAs) emerge as pivotal players in modulating immune cell functions and tumor growth. We also discuss ongoing clinical trials that explore metabolic modulation for PDAC, targeting mitochondrial metabolism, asparagine and glutamine addiction, and autophagy inhibition. Overcoming challenges in understanding nutrient effects on immune-stromal-tumor interactions holds promise for innovative therapeutic strategies.