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Therapeutic potential of statins in thyroid proliferative disease

Nature Clinical Practice Endocrinology & Metabolism volume 4, pages 242–243 (2008)Cite this article

The thyroid gland is a frequent site of abnormal epithelial cell proliferation. Proliferative diseases of the thyroid follicular cells that arise as either sporadic or nontoxic multinodular goiter progress to neoplasia in ∼5% of all cases. In addition, the incidence of thyroid cancer has risen rapidly over the past few years. In terms of histology, this endocrine malignancy predominantly comprises papillary thyroid cancer and follicular thyroid cancer, whereas medullary thyroid cancer and anaplastic thyroid cancer (ATC) occur less frequently. Nonetheless, ATC is considered one of the most aggressive forms of human neoplasia and is refractory to conventional therapeutic strategies. Innovative approaches are, therefore, currently underway to investigate novel treatments for thyroid proliferative disease. For example, statins have been reported to affect proliferation and survival of several tumor cell types (including thyroid) and display in vivo antitumor activity when used as single agents or in combination with other anticancer drugs.

Statins are cholesterol-lowering agents that are commonly prescribed to prevent cardiovascular and coronary heart disease. These drugs inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of isoprenoid and cholesterol biosynthesis. Inhibition of this enzyme prevents the reduction of HMG-CoA to mevalonate, the precursor of cholesterol. In addition to their lipid-lowering properties, statins are also thought to display immunomodulatory, anti-inflammatory, and antioxidant activity, and to reduce insulin resistance and progression of renal disease. These effects do not seem to be directly related to inhibition of cholesterol biosynthesis. Mevalonate is also the precursor of prenyl groups, which are transferred by farnesyl and geranylgeranyl transferases to small guanosine triphosphate-binding proteins of the Ras and Rho families. Protein prenylation is essential for anchoring these proteins to the plasma membrane and for subsequent activation of proteins involved in cellular proliferation, adhesion, and motility.

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Acknowledgements

The author's work is supported by the Associazione Educazione e Ricerca Medica Salernitana (ERMES).

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  1. Department of Pharmaceutical Sciences, University of Salerno, Via Ponte Don Melillo, 84084 Fisciano (Salerno), Italy maubiful@unisa.it

Authors and Affiliations

  1. M Bifulco is Full Professor of General Pathology in the Department of Pharmaceutical Sciences, University of Salerno, Italy.,

    Maurizio Bifulco

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Bifulco, M. Therapeutic potential of statins in thyroid proliferative disease. Nat Rev Endocrinol 4, 242–243 (2008). https://doi.org/10.1038/ncpendmet0782

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