REVIEW article
Front. Oncol.
Sec. Cancer Cell Signaling
This article is part of the Research TopicTargeted Cancer Therapy Through Metabolic PathwaysView all 4 articles
HMGCR: A Malignancy Hub - Frontiers in Cancer Diagnosis and Therapy
Provisionally accepted
- Experimental Center, Dalian University, Dalian, China
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Cholesterol metabolism is significantly activated during most tumor growth. As a key rate-limiting enzyme in cholesterol synthesis, HMG-CoA reductase (HMGCR) affects tumor metabolic reprogramming by upregulating cholesterol metabolism and promotes tumor growth and immune escape by remodeling the tumor microenvironment. It fuels tumor growth by providing cholesterol and isoprenoids, regulating critical pathways (Hippo, Hedgehog, MAPK), and modulating ferroptosis sensitivity. A complex bidirectional relationship exists between HMGCR and the pro-inflammatory cytokine TNF-α: TNF-α can inhibit HMGCR activity and thus inhibit cholesterol synthesis. At the same time, HMGCR influences TNF-α mediated inflammation and immune evasion. Statins, as HMGCR inhibitors, have shown anti-tumor effects in experiments. However, clinical application faces challenges including highly toxic concentration, drug resistance and tissue specificity. Accordingly, further exploration of mechanism-based targeted precision therapies to intervene in the HMGCR-TNF-α axis and related pathways, as well as the development of novel HMGCR inhibitors or optimization of existing drugs, represents an innovative strategy to enhance cancer treatment efficacy and advance drug development.
Keywords: cholesterol metabolism, HMGCR, Tumor Microenvironment, Signal pathways, TNF-α
Received: 03 Sep 2025; Accepted: 24 Nov 2025.
Copyright: © 2025 Yang, Liu, Zou, Liu, Zhou, Tao and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Xingzhi Zhou
Ran Tao
Shuangping Liu
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