Sterol synthesis pathway inhibition as a target for cancer treatment.

Abstract

Sterol synthesis is a highly complex and integrated pathway in mammals. In the present review, we briefly summarize the main steps of this pathway, especially concerning its main rate-limiting enzymes, HMG-CoA reductase (HMGCR) and squalene epoxidase (SQLE), in relation with cancer. We focus on studies reporting key findings linking cholesterol with cancer. The inhibition of HMGCR and SQLE to prevent and inhibit cancer are reviewed. Finally, a pan-cancer review of publicly available data on genomic aberrations in the main enzymes involved in sterol biosynthesis and their transcription factors is reported, providing hitherto unexplored findings that may be the subject of future research in cancer metabolomics and tumor targeted treatment.

• Authors: Sara Feltrin, Francesco Ravera, Noemi Traversone, Lorenzo Ferrando, Davide Bedognetti, Alberto Ballestrero, Gabriele Zoppoli
• Journal: Cancer letters (Cancer Lett) Vol. 493 Pg. 19-30 (11 28 2020) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 32711099 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Antineoplastic Agents
• Transcription Factors
• Cholesterol
• HMGCR protein, human
• Hydroxymethylglutaryl CoA Reductases
• Squalene Monooxygenase

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Biosynthetic Pathways (drug effects)
• Cholesterol (biosynthesis)
• Humans
• Hydroxymethylglutaryl CoA Reductases (metabolism)
• Molecular Targeted Therapy
• Neoplasms (drug therapy, genetics, metabolism)
• Squalene Monooxygenase (metabolism)
• Transcription Factors (genetics)