Title:Targeting Mevalonate Pathway in Cancer Treatment: Repurposing of Statins
Volume: 13
Issue: 2
Author(s): Federica Iannelli, Rita Lombardi, Maria R. Milone, Biagio Pucci, Simona De Rienzo, Alfredo Budillon*Francesca Bruzzese*
Affiliation:
- Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples,Italy
- Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples,Italy
Keywords:
Cancer, HMG-CoA reductase (HMGCR), mevalonate pathway (MVP), MVP inhibitors, repurposing, statins, statins
antitumor effect.
Abstract: Background: Modifications of lipid metabolism have been progressively accepted as a hallmark
of tumor cells and in particular, an elevated lipogenesis has been described in various types of
cancers.
Objective: Important or deregulated activity of the mevalonate pathway has been demonstrated in different
tumors and a wide range of studies have suggested that tumor cells are more dependent on the
unceasing availability of mevalonate pathway metabolites than their non-malignant complements.
Methods: This study provides an overview of the state of the art of statins treatment on human cancer.
Results: In recent times, various actions have been proposed for statins in different physiological and
pathological conditions beyond anti-inflammation and neuroprotection activity.
Statins have been shown to act through mevalonate-dependent and -independent mechanisms able to
affect several tissue functions and modulating specific signal transduction pathways that could account
for statin pleiotropic effect.
Based on their characteristics, statins represent ideal candidates for repositioning in cancer therapy.
Conclusion: In this review article, we provide an overview of the current preclinical and clinical status
of statins as antitumor agents. In addition, we evaluated various patents that describe the role of mevalonate
pathway inhibitors and methods to determine if cancer cells are sensitive to statins treatment.
