ReviewPharmacology & therapeutics2014
Targeting the mevalonate cascade as a new therapeutic approach in heart disease, cancer and pulmonary disease.
Review in Pharmacology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
81 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.
- Molecular Signature in Focal Cortical Dysplasia: A Systematic Review of RNA and Protein Data.International journal of molecular sciences · 2025Pooled it
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- The Mevalonate Pathway: Innovations, Applications, and Challenges in Biotechnology with Emphasis on Fungal Biology.Journal of fungi (Basel, Switzerland) · 2026Review
- Emerging roles of the metabolic regulator 3-hydroxy-3-methylglutaryl coenzyme-CoA reductase in human cancers: From biology to therapeutics.Genes & diseases · 2026Review
- FABP7 controls radial glial scaffold stability during human cortical development.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The impact of lipid metabolism remodeling in the tumor microenvironment on angiogenesis.Discover oncology · 2026Review
- Mevalonic acid exerts procoagulant effect by potentiating factor Xa.Natural products and bioprospecting · 2026Article
- Metabolic Pathway Analysis in Chicken Induced by Selenium-Enriched Yeast: Insights from Flavoromics and Metabolomics.Foods (Basel, Switzerland) · 2025Article
- Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.The FEBS journal · 2025Article
- Molecular and Immunomodulatory Mechanisms of Statins in Inflammation and Cancer Therapeutics with Emphasis on the NF-κB, NLRP3 Inflammasome, and Cytokine Regulatory Axes.International journal of molecular sciences · 2025Review
- Repurposing a Lipid-Lowering Agent to Inhibit TNBC Growth Through Cell Cycle Arrest.Current issues in molecular biology · 2025Article
- Statins exhibit anti-tumor potential by modulating Wnt/β-catenin signaling in colorectal cancer.Oncotarget · 2025Article
- Exploring breath metabolomics as a non-invasive tool for detecting pulmonary vascular disease.European heart journal open · 2025Article
- Increased SOAT2 expression in aged regulatory T cells is associated with altered cholesterol metabolism and reduced anti-tumor immunity.Nature communications · 2025Article
- Bidirectional regulation of lipid metabolism and the tumor microenvironment: new perspectives from mechanism to therapy.Frontiers in immunology · 2025Review
- Pulmonary hypertension: etiology and anti-inflammatory treatment pathways of natural products.Frontiers in pharmacology · 2025Review
- Simvastatin Overcomes Resistance to Tyrosine Kinase Inhibitors in Patient-derived, Oncogene-driven Lung Adenocarcinoma Models.Molecular cancer therapeutics · 2024Article
- Statins as anti-tumor agents: A paradigm for repurposed drugs.Cancer reports (Hoboken, N.J.) · 2024Review
- Obesity-associated Airway Hyperresponsiveness: Mechanisms Underlying Inflammatory Markers and Possible Pharmacological Interventions.Endocrine, metabolic & immune disorders drug targets · 2024Review
- Mechanisms of 3-Hydroxyl 3-Methylglutaryl CoA Reductase in Alzheimer's Disease.International journal of molecular sciences · 2023Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 9 institutions in 4 countries.
Funding
Abstract
The cholesterol biosynthesis pathway, also known as the mevalonate (MVA) pathway, is an essential cellular pathway that is involved in diverse cell functions. The enzyme 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGCR) is the rate-limiting step in cholesterol biosynthesis and catalyzes the conversion of HMG-CoA to MVA. Given its role in cholesterol and isoprenoid biosynthesis, the regulation of HMGCR has been intensely investigated. Because all cells require a steady supply of MVA, both the sterol (i.e. cholesterol) and non-sterol (i.e. isoprenoid) products of MVA metabolism exert coordinated feedback regulation on HMGCR through different mechanisms. The proper functioning of HMGCR as the proximal enzyme in the MVA pathway is essential under both normal physiologic conditions and in many diseases given its role in cell cycle pathways and cell proliferation, cholesterol biosynthesis and metabolism, cell cytoskeletal dynamics and stability, cell membrane structure and fluidity, mitochondrial function, proliferation, and cell fate. The blockbuster statin drugs ('statins') directly bind to and inhibit HMGCR, and their use for the past thirty years has revolutionized the treatment of hypercholesterolemia and cardiovascular diseases, in particular coronary heart disease. Initially thought to exert their effects through cholesterol reduction, recent evidence indicates that statins also have pleiotropic immunomodulatory properties independent of cholesterol lowering. In this review we will focus on the therapeutic applications and mechanisms involved in the MVA cascade including Rho GTPase and Rho kinase (ROCK) signaling, statin inhibition of HMGCR, geranylgeranyltransferase (GGTase) inhibition, and farnesyltransferase (FTase) inhibition in cardiovascular disease, pulmonary diseases (e.g. asthma and chronic obstructive pulmonary disease (COPD)), and cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.