TY - JOUR
T1 - Mechanisms and Implications of Metabolic Heterogeneity in Cancer
AU - Kim, Jiyeon
AU - DeBerardinis, Ralph J.
N1 - Funding Information:
The rapid growth of research in cancer metabolism made it impossible to cite a large number of excellent studies relevant to the topic of this review. We are grateful to Katie Regan for help with the figures. R.J.D. is supported by the Howard Hughes Medical Institute, the National Cancer Institute (R35CA22044901), and the Moody Foundation (Robert L. Moody Faculty Scholar Award). J.K. is supported by the National Cancer Institute (1K22CA226676-01A1) and American Lung Association (LCD-614827). R.J.D. is an advisor for Agios Pharmaceuticals and holds shares in Agios Pharmaceuticals and Peloton Therapeutics.
Funding Information:
The rapid growth of research in cancer metabolism made it impossible to cite a large number of excellent studies relevant to the topic of this review. We are grateful to Katie Regan for help with the figures. R.J.D. is supported by the Howard Hughes Medical Institute , the National Cancer Institute ( R35CA22044901 ), and the Moody Foundation (Robert L. Moody Faculty Scholar Award). J.K. is supported by the National Cancer Institute ( 1K22CA226676-01A1 ) and American Lung Association ( LCD-614827 ).
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/9/3
Y1 - 2019/9/3
N2 - Tumors display reprogrammed metabolic activities that promote cancer progression. We currently possess a limited understanding of the processes governing tumor metabolism in vivo and of the most efficient approaches to identify metabolic vulnerabilities susceptible to therapeutic targeting. While much of the literature focuses on stereotyped, cell-autonomous pathways like glycolysis, recent work emphasizes heterogeneity and flexibility of metabolism between tumors and even within distinct regions of solid tumors. Metabolic heterogeneity is important because it influences therapeutic vulnerabilities and may predict clinical outcomes. This Review describes current concepts about metabolic regulation in tumors, focusing on processes intrinsic to cancer cells and on factors imposed upon cancer cells by the tumor microenvironment. We discuss experimental approaches to identify subtype-selective metabolic vulnerabilities in preclinical cancer models. Finally, we describe efforts to characterize metabolism in primary human tumors, which should produce new insights into metabolic heterogeneity in the context of clinically relevant microenvironments. Tumors display substantial metabolic heterogeneity and flexibility. This review discusses convergent and divergent metabolic properties in tumors, and how factors intrinsic and extrinsic to malignant cells establish metabolic phenotypes in the tumor microenvironment. Understanding these concepts will help us develop strategies to capitalize on metabolic reprogramming in cancer treatment.
AB - Tumors display reprogrammed metabolic activities that promote cancer progression. We currently possess a limited understanding of the processes governing tumor metabolism in vivo and of the most efficient approaches to identify metabolic vulnerabilities susceptible to therapeutic targeting. While much of the literature focuses on stereotyped, cell-autonomous pathways like glycolysis, recent work emphasizes heterogeneity and flexibility of metabolism between tumors and even within distinct regions of solid tumors. Metabolic heterogeneity is important because it influences therapeutic vulnerabilities and may predict clinical outcomes. This Review describes current concepts about metabolic regulation in tumors, focusing on processes intrinsic to cancer cells and on factors imposed upon cancer cells by the tumor microenvironment. We discuss experimental approaches to identify subtype-selective metabolic vulnerabilities in preclinical cancer models. Finally, we describe efforts to characterize metabolism in primary human tumors, which should produce new insights into metabolic heterogeneity in the context of clinically relevant microenvironments. Tumors display substantial metabolic heterogeneity and flexibility. This review discusses convergent and divergent metabolic properties in tumors, and how factors intrinsic and extrinsic to malignant cells establish metabolic phenotypes in the tumor microenvironment. Understanding these concepts will help us develop strategies to capitalize on metabolic reprogramming in cancer treatment.
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U2 - 10.1016/j.cmet.2019.08.013
DO - 10.1016/j.cmet.2019.08.013
M3 - Review article
C2 - 31484055
AN - SCOPUS:85070895202
SN - 1550-4131
VL - 30
SP - 434
EP - 446
JO - Cell Metabolism
JF - Cell Metabolism
IS - 3
ER -