Metabolic isoenzyme shifts in cancer as potential novel therapeutic targets.
The functional redundancy of metabolic enzyme expression may present a new strategy for developing targeted therapies in cancer. To satisfy the increased metabolic demand required during neoplastic transformations and proliferation, cancer cells may rely on additional isoforms of a metabolic enzyme to satisfy the increased demand for metabolic precursors, which could subsequently render cancer cells more vulnerable to isoform-specific inhibitors. In this review, we provide a survey of common isoenzyme shifts that have been reported to be important in cancer metabolism and link those to metabolic pathways that currently have drugs in various stages of development. This phenomenon suggests a potentially new therapeutic strategy for the treatment of cancer by identifying shifts in the expression of metabolic isoenzymes between cancer and normal cells. We also delineate other putative metabolic isoenzymes that could be targets for novel targeted therapies for cancer. Changes in isoenzyme expression that occur during neoplastic transformations or in response to environmental pressure in cancer cells may result in isoenzyme diversity that may subsequently render cancer cells more vulnerable to isoform-specific inhibitors due to reliance on a single isoform to perform a vital enzymatic function.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, 06511, USA, sophia.ononye@yale.edu.
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SN
Ononye
W
W
Shi
V B
VB
Wali
B
B
Aktas
T
T
Jiang
C
C
Hatzis
L
L
Pusztai
D030562:Databases, Protein; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy
D004791:Enzyme Inhibitors; D007527:Isoenzymes