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Inhibition of glutaminolysis in combination with other therapies to improve cancer treatment.

Abstract
Targeting glutamine catabolism has been attracting more research attention on the development of successful cancer therapy. Catalytic enzymes such as glutaminase (GLS) in glutaminolysis, a series of biochemical reactions by which glutamine is converted to glutamate and then alpha-ketoglutarate, an intermediate of the tricarboxylic acid (TCA) cycle, can be targeted by small molecule inhibitors, some of which are undergoing early phase clinical trials and exhibiting promising safety profiles. However, resistance to glutaminolysis targeting treatments has been observed, necessitating the development of treatments to combat this resistance. One option is to use synergy drug combinations, which improve tumor chemotherapy's effectiveness and diminish drug resistance and side effects. This review will focus on studies involving the glutaminolysis pathway and diverse combination therapies with therapeutic implications.
AuthorsYao-An Shen, Chi-Long Chen, Yi-Hsuan Huang, Emily Elizabeth Evans, Chun-Chia Cheng, Ya-Jie Chuang, Cissy Zhang, Anne Le
JournalCurrent opinion in chemical biology (Curr Opin Chem Biol) Vol. 62 Pg. 64-81 (06 2021) ISSN: 1879-0402 [Electronic] England
PMID33721588 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
CopyrightCopyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Ketoglutaric Acids
  • Glutamine
  • Lactic Acid
  • Glycogen
  • Glutaminase
Topics
  • Animals
  • Antineoplastic Agents (chemistry, metabolism, pharmacology)
  • Antineoplastic Combined Chemotherapy Protocols (chemistry, metabolism, pharmacology)
  • Apoptosis (drug effects)
  • Cell Line, Tumor
  • Citric Acid Cycle (drug effects)
  • Drug Resistance, Neoplasm (drug effects)
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors (chemistry, metabolism)
  • Glutaminase (antagonists & inhibitors, metabolism)
  • Glutamine (metabolism)
  • Glycogen (chemistry, metabolism)
  • Humans
  • Ketoglutaric Acids (metabolism)
  • Lactic Acid (chemistry, metabolism)
  • Signal Transduction

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