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Targeting cancer metabolism

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Teicher, Beverly A., Linehan, W. Marston, Helman, Lee J.·2012·Clinical Cancer Research
DOI 10.1158/1078-0432.ccr-12-2587PMC PMC3475613
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Abstract

The understanding that oncogenes can have profound effects on cellular metabolism and the discovery of mutations and alterations in several metabolism-related enzymes--isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2), succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (PKM2)--has renewed interest in cancer metabolism and renewed hope of taking therapeutic advantage of cancer metabolism. Otto Warburg observed that aerobic glycolysis was a characteristic of cancer cells. More than 50 years later, we understand that aerobic glycolysis and uptake of glutamine and glycine allow cancer cells to produce energy (ATP) and the nucleotides, amino acids, and lipids required for proliferation. Expression of the MYC oncogene drives the increase in cellular biomass facilitating proliferation. PKM2 expression in cancer cells stimulates aerobic glycolysis. Among intermediary metabolism enzymes, mutations in SDH occur in gastointestinal stromal tumors and result in a pseudohypoxic metabolic milieu. FH mutations lead to a characteristic renal cell carcinoma. Isocitrate dehydrogenase (IDH1/2) mutations have been found in leukemias, gliomas, prostate cancer, colon cancer, thyroid cancer, and sarcomas. These recently recognized oncogenic metabolic lesions may be selective targets for new anticancer therapeutics.

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  • Metabolic reprogramming is a hallmark of cancer based on the discovery of mutations and alterations in IDH1 and IDH2 along with SDH, FH, and PKM2.

    “There is a renewed interest in the area of cancer metabolism with metabolic reprogramming coined as a hallmark of cancer based on the discovery of mutations and alterations in IDH1 and IDH2 along with succinate dehydrogenase (SDH), fumarate hydratase (FH), and pyruvate kinase M2 (PKM2) [41, 42].”

    From Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells (2018) · cites this paper as [41]

    The Abstract names IDH1, IDH2, SDH, FH, and PKM2 and says discoveries involving these enzymes renewed interest in cancer metabolism. The Introduction (“Cancer requires Specific Metabolic Programming for Proliferation”) makes the same point, but neither passage says metabolic reprogramming was coined a hallmark of cancer on that basis. No page numbers are provided in our copy. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Teicher, B. A., Linehan, W. M., & Helman, L. J.
Affiliations
National Cancer Institute (US)
Corresponding author
Teicher, Beverly A.
ORCID
Venue
Clinical Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2012-10-14
Volume
18
Issue
20
Pages
5537-5545
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
DOI
10.1158/1078-0432.ccr-12-2587
PMC
PMC3475613
OpenAlex
W2147047620
Cited by
152
References
20
Citations by year
2026: 4 · 2025: 12 · 2024: 4 · 2023: 7 · 2022: 15 · 2021: 9 · 2020: 6 · 2019: 15 · 2018: 12 · 2017: 8 · 2016: 7 · 2015: 21 · 2014: 16 · 2013: 13 · 2012: 3
FWCI
5.63
Type
journal article
Language
en
Open access
Locations
  • Clinical Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (Z99 CA999999)
  • National Cancer Institute (Y99 CA999999, ZIABC011038, ZIABC011028)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
cancer metabolism, aerobic glycolysis, Warburg effect, glutamine uptake, glycine metabolism, MYC oncogene, PKM2, IDH mutation, succinate dehydrogenase, fumarate hydratase, pseudohypoxia, renal cell carcinoma, anticancer agents
MeSH terms
Fumarate Hydratase, Glycolysis, Humans, Isocitrate Dehydrogenase, Mutation, Neoplasms, Pyruvate Kinase, Succinate Dehydrogenase, Cell Proliferation, Molecular Targeted Therapy

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