The mevalonate pathway in breast cancer biology

Cancer Lett. 2022 Aug 28:542:215761. doi: 10.1016/j.canlet.2022.215761. Epub 2022 May 28.

Abstract

Breast cancer affects one in eight women during their lifetime. Although diagnostic and therapeutic options have improved, recurrence, metastasis, and therapeutic resistance remain clinical challenges, which affect life quality and prognosis. The mevalonate pathway is an essential part of cellular homeostasis by providing a number of essential isoprenoid products including cholesterol. However, the disturbance of this pathway paralleled by increased bioavailability of its products and their direct involvement in several steps of tumorigenesis has highlighted the mevalonate pathway as a promising hub in cancer treatment. In this review, we will specifically discuss how the mevalonate pathway affects breast cancer biology in terms of supporting and modulating soluble and cellular factors and distinct steps of tumorigenesis. We will further summarize antitumor effects of the mevalonate pathway-inhibiting drugs, statins and amino-bisphosphonates, in breast cancer and discuss how they are used for future precision therapy.

Keywords: Amino-bisphosphonates; Breast cancer; Cholesterol; Rho-GTPases; Statins.

Publication types

  • Review

MeSH terms

  • Biology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Cell Transformation, Neoplastic
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Mevalonic Acid / metabolism

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Mevalonic Acid