Targeting cellular metabolism to improve cancer therapeutics

By Y. Zhao, E. B. Butler, Ming Tan. Cell Death and Disease, 2013

970 citations recorded by the source corpus.

The metabolic properties of cancer cells diverge significantly from those of normal cells. Energy production in cancer cells is abnormally dependent on aerobic glycolysis. In addition to the dependency on glycolysis, cancer cells have other atypical metabolic characteristics such as increased fatty acid synthesis and increased rates of glutamine metabolism. Emerging evidence shows that many features characteristic to cancer cells, such as dysregulated Warburg-like glucose metabolism, fatty acid synthesis and glutaminolysis are linked to therapeutic resistance in cancer treatment. Therefore, targeting cellular metabolism may improve the response to cancer therapeutics and the combination of chemotherapeutic drugs with cellular metabolism inhibitors may represent a promising strategy to overcome drug resistance in cancer therapy. Recently, several review articles have summarized the anticancer targets in the metabolic pathways and metabolic inhibitor-induced cell death pathways, however, the dysregulated metabolism in therapeutic resistance, which is a highly clinical relevant area in cancer metabolism research, has not been specifically addressed. From this unique angle, this review article will discuss the relationship between dysregulated cellular metabolism and cancer drug resistance and how targeting of metabolic enzymes, such as glucose transporters, hexokinase, pyruvate kinase M2, lactate dehydrogenase A, pyruvate dehydrogenase kinase, fatty acid synthase and glutaminase can enhance the efficacy of common therapeutic agents or overcome resistance to chemotherapy or radiotherapy.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ad70f9f309102faa5dc81be6ad1db34ba825f21a

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Citations in the corpus

Tumor glycolysis as a target for cancer therapy: progress and prospects (2013, background): “Several authors have delineated a wealth of information on the biochemical targets of glycolysis and their potent antagonists or inhibitors with promising anticancer effects (refer reviews [14-18]).”
Targeting Metabolism for Cancer Therapy (2017, background): “Substantial work has sought to target increased glycolysis including efforts to inhibit lactate production and excretion (Doherty and Cleveland, 2013; Hamanaka and Chandel, 2012; Hay, 2016; Pelicano et al., 2006; Zhao et al., 2013).”
Regulation of pyruvate metabolism and human disease (2013, background): “As discussed above, the generation of lactate is critically important to cancer cell metabolism and survival, both of which would be impaired by LDHA inhibition [169].”