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Targeting Mevalonate Pathway in Cancer Treatment: Repurposing of Statins

[ Vol. 13 , Issue. 2 ]

Author(s):

Federica Iannelli, Rita Lombardi, Maria R. Milone, Biagio Pucci, Simona De Rienzo, Alfredo Budillon* and Francesca Bruzzese*   Pages 184 - 200 ( 17 )

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.

Keywords:

Cancer, HMG-CoA reductase (HMGCR), mevalonate pathway (MVP), MVP inhibitors, repurposing, statins, statins antitumor effect.

Affiliation:

Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Mercogliano Oncology Research Center (CROM), Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Mercogliano Oncology Research Center (CROM), Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Mercogliano Oncology Research Center (CROM), Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples, Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazione Giovanni Pascale - IRCCS, 80131 Naples



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