Abstract IA016: Metabolic reprogramming and cancer progression in patients

Abstract Many human diseases, including cancer, involve alterations of cellular metabolism caused either directly or indirectly by mutations in genes that regulate the metabolic network. In cancer, reprogrammed metabolic activities arising from mutations in tumor suppressors and oncogenes are thought to contribute both to cancer initiation and progression, particularly metastasis. Many factors intrinsic or extrinsic to the cancer cell impact metabolic properties within tumors and influence vulnerabilities that could presumably be exploited to suppress cancer progression. Although many insights about metabolic regulation have been derived from reductionist models of cancer cell growth in culture, these models do not incorporate all of the factors – particularly cancer cell-extrinsic factors – that contribute to cancer progression. I will describe approaches to assess cancer metabolism within intact tumors, including in cancer patients. We use a multidisciplinary approach to infuse 13C-labeled nutrients (13C-glucose, 13C-acetate, 13C-glutamine) during surgical tumor resection in patients with malignancies in the brain, lung, kidney and other organs. Isotope labeling in metabolites extracted from tumors and adjacent, nonmalignant tissue provides information metabolic pathways activated or repressed in the tumors. By following clinical outcomes over time, we have identified labeling features and pathways that correlate with metastasis and early demise. I will discuss how these features reflect the evolution of metabolic properties and liabilities during human cancer progression, and how parallel studies in mice have allowed us to define mechanisms by metabolism supports metastasis. Citation Format: Ralph J. DeBerardinis. Metabolic reprogramming and cancer progression in patients abstract. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84 (5 Suppl₁): Abstract nr IA016.