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Targeting tumor cell metabolism via the mevalonate pathway: Two hits are better than one

Aleksandra Pandyra1, Linda Z Penn1

  • 1Princess Margaret Cancer Centre, Toronto, ON, Canada; Department of Medical Biophysics; University of Toronto ; Toronto, ON, Canada.

Molecular & Cellular Oncology
|June 17, 2016
PubMed

Insights

Statins show anticancer promise by targeting the mevalonate pathway. Combining statins with dipyridamole overcomes tumor cell resistance, enhancing their antitumor effects.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Statins are cholesterol-lowering drugs with potential anticancer properties.
  • Statins target the mevalonate pathway, crucial for tumor cell proliferation.
  • Tumor cells develop resistance to statins via a feedback loop, limiting their efficacy.

Purpose of the Study:

  • To investigate the potential of combining statins with dipyridamole to enhance anticancer activity.
  • To elucidate the mechanism by which dipyridamole overcomes statin resistance.

Main Methods:

  • Preclinical studies evaluating the combined efficacy of statins and dipyridamole.
  • Analysis of the mevalonate pathway feedback loop in tumor cells.

Main Results:

  • Dipyridamole was found to inhibit the homeostatic feedback loop that blunts statin efficacy.
  • The combination of statins and dipyridamole demonstrated potentiated antitumor activity in preclinical models.
  • This combination utilizes approved agents for potential therapeutic application.

Conclusions:

  • Statins plus dipyridamole represent a promising combination therapy for cancer treatment.
  • Targeting the mevalonate pathway feedback loop is a viable strategy to enhance statin antitumor effects.
  • This combination offers a potential new therapeutic approach leveraging existing drugs.
Keywords:
HMG-CoA ReductaseMevalonateSREBP2dipyridamolestatins

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