TY - JOUR
T1 - Targeting cancer metabolism
AU - Teicher, Beverly A.
AU - Linehan, W. Marston
AU - Helman, Lee J.
PY - 2012/10/15
Y1 - 2012/10/15
N2 - 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. PKM2expression 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.
AB - 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. PKM2expression 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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U2 - 10.1158/1078-0432.CCR-12-2587
DO - 10.1158/1078-0432.CCR-12-2587
M3 - Review article
C2 - 23071355
AN - SCOPUS:84867518730
SN - 1078-0432
VL - 18
SP - 5537
EP - 5545
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 20
ER -