Abstract IA23: Metabolic complexity in cancer cells and tumors

Abstract

Abstract Metabolism is dynamic and responds to a wide range of cell-intrinsic and cell-extrinsic factors. In cancer, cell-intrinsic influences on metabolism include somatically acquired mutations in oncogenes and tumor suppressor genes, many of which regulate metabolic activity. Cell-extrinsic factors include nutrient access, which may become limiting due to inadequate vasculature and intense fuel utilization, and metabolic interactions with stromal and immune cells. A major challenge in cancer metabolism research is to understand how these various factors culminate in the metabolic phenotype of an intact tumor, and ultimately to identify which altered pathways represent potential therapeutic targets. We have taken two parallel approaches to understand metabolic complexity in human cancer. The first uses a combination of multiparametric imaging and intraoperative stable isotope infusions to assess metabolic fluxes in patients with solid tumors, and to compare fluxes between tumors and adjacent benign tissue. Genomic, histologic, and metabolic analysis of tumor samples allows us to correlate various intrinsic and extrinsic factors to specific aspects of the metabolic phenotype. The second approach uses standardized culture conditions to assess cell-intrinsic heterogeneity of metabolic preferences and dependencies in large panels of human cancer cell lines. This approach has uncovered liabilities associated with specific molecular subtypes of non-small cell and small cell lung cancer. I will discuss the application of these two approaches to metabolic heterogeneity in human cancer, with an emphasis on features relevant to intact tumors and therapeutic liabilities. Citation Format: Ralph J. DeBerardinis. Metabolic complexity in cancer cells and tumors [abstract]. In: Proceedings of the AACR Special Conference: Pediatric Cancer Research: From Basic Science to the Clinic; 2017 Dec 3-6; Atlanta, Georgia. Philadelphia (PA): AACR; Cancer Res 2018;78(19 Suppl):Abstract nr IA23.