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Abstract IA21: Metabolic phenotypes and liabilities in human cancer

Metabolic reprogramming in cancer arises from a complex, incompletely-defined combination of factors intrinsic and extrinsic to malignant cells. In some cases, reprogrammed pathways contribute to the process of transformation, and in many others they enable cancer progression by supporting cell survival and excessive growth. The clinical relevance of cancer metabolism is emphasized by the fact that numerous imaging modalities and therapeutic strategies in cancer capitalize on the altered metabolic states present in tumors. Recent work has emphasized that metabolic phenotypes and liabilities evolve as cancer progresses, such that pathways required for cancer initiation may be dispensable in more advanced stages, and vice versa. A key challenge is to define metabolic properties that support key aspects of cancer progression, particularly metastasis and acquired therapy resistance, which account for the majority of cancer-related deaths. Because these processes are difficult to model in culture, we have developed clinical approaches to study cancer metabolism in vivo, in patients, and to uses these approaches to identify features that drive cancer progression. I will discuss approaches using metabolomics and intra-operative infusions with 13C-labeled nutrients to assess metabolic pathway utilization in human tumors. We use this approach to characterize metabolic heterogeneity among tumors arising in different organs, to identify areas of regional metabolic heterogeneity within solid tumors and to predict which activities support cancer progression. Our work to this point demonstrates marked diversity of fuel preferences in primary tumors and unexpected roles of particular pathways in cancer cell biology. Citation Format: Ralph J. DeBerardinis. Metabolic phenotypes and liabilities in human cancer [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA21.