Nature and Nurture: What Determines Tumor Metabolic Phenotypes?

Cancer Res
Authors
Keywords
Abstract

Understanding the genetic basis of cancer has led to therapies that target driver mutations and has helped match patients with more personalized drugs. Oncogenic mutations influence tumor metabolism, but other tumor characteristics can also contribute to their metabolic phenotypes. Comparison of isogenic lung and pancreas tumor models suggests that use of some metabolic pathways is defined by lineage rather than by driver mutation. Lung tumors catabolize circulating branched chain amino acids (BCAA) to extract nitrogen for nonessential amino acid and nucleotide synthesis, whereas pancreatic cancer obtains amino acids from catabolism of extracellular protein. These differences in amino acid metabolism translate into distinct pathway dependencies, as genetic disruption of the enzymes responsible for utilization of BCAA nitrogen limits the growth of lung tumors, but not pancreatic tumors. These data argue that some cancer metabolic phenotypes are defined by cancer tissue-of-origin and environment and that these features constrain the influence of genetic mutations on metabolism. A better understanding of the factors defining tumor nutrient utilization could be exploited to help improve cancer therapy. .

Year of Publication
2017
Journal
Cancer Res
Volume
77
Issue
12
Pages
3131-3134
Date Published
2017 06 15
ISSN
1538-7445
DOI
10.1158/0008-5472.CAN-17-0165
PubMed ID
28584183
Links
Grant list
F30 CA183474 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
R01 CA168653 / CA / NCI NIH HHS / United States
R01 CA201276 / CA / NCI NIH HHS / United States