Statins Limit Coenzyme Q Synthesis and Metabolically Synergize with MEK Inhibition in Pancreatic Tumors

Cancer Res. 2020 Jan 15;80(2):151-152. doi: 10.1158/0008-5472.CAN-19-3415.

Abstract

Tumors frequently increase expression of enzymes in the mevalonate biosynthesis pathway. Statins inhibit flux through this pathway, but if and how such treatments elicit a therapeutic benefit in cancer remains unclear. In this issue of Cancer Research, McGregor and colleagues perform in vivo metabolic tracing to demonstrate that mouse pancreatic ductal adenocarcinoma (PDAC) tumors and human PDAC cell lines require this pathway for coenzyme Q (CoQ) synthesis and redox homeostasis. Simvastatin treatment reduces CoQ synthesis and promotes oxidative stress and apoptosis in tumors when administered in combination with a MEK inhibitor, providing a new mechanism through which statin treatment may impact PDAC growth.See related article by McGregor et al., p. 175.

Publication types

  • Research Support, N.I.H., Extramural
  • Comment

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Mice
  • Oxidative Stress
  • Pancreatic Neoplasms*
  • Ubiquinone

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ubiquinone