Trends in Cancer
Volume 6, Issue 11, November 2020, Pages 942-950
Journal home page for Trends in Cancer

Opinion
Targeting EMT in Cancer with Repurposed Metabolic Inhibitors

https://doi.org/10.1016/j.trecan.2020.06.005Get rights and content
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Highlights

  • Epithelial-to-mesenchymal transition (EMT), an embryonic phenotypic plasticity program, in cancer confers invasiveness, dissemination, and chemo/immunotherapy resistance.

  • EMT drives through dynamic intermediate states (partial EMT), which possess high metastasis-initiating potential. Genomic and functional analyses have determined the existence of EMT/partial EMT features in multiple human cancer types.

  • EMT is associated with significant metabolic rewiring, and some metabolic pathways promote and maintain EMT.

  • Repurposing of antimetabolism drugs in EMT-driven cancers could reduce the incidence of metastasis and improve patients’ response to treatments.

  • A better understanding of the interdependence between EMT and metabolism could accelerate the discovery of novel treatments for aggressive cancers.

Epithelial-to-mesenchymal transition (EMT) determines the most lethal features of cancer, metastasis formation and chemoresistance, and therefore represents an attractive target in oncology. However, direct targeting of EMT effector molecules is, in most cases, pharmacologically challenging. Since emerging research has highlighted the distinct metabolic circuits involved in EMT, we propose the use of metabolism-specific inhibitors, FDA approved or under clinical trials, as a drug repurposing approach to target EMT in cancer. Metabolism-inhibiting drugs could be coupled with standard chemo- or immunotherapy to combat EMT-driven resistant and aggressive cancers.

Keywords

epithelial–mesenchymal transition
partial EMT
metabolic inhibitor
drug repurposing
chemoresistance

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