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Advanced medullary thyroid cancer: pathophysiology and management

Authors Ferreira CV, Siqueira DR, Ceolin L, Maia AL

Received 26 February 2013

Accepted for publication 25 March 2013

Published 8 May 2013 Volume 2013:5 Pages 57—66

DOI https://doi.org/10.2147/CMAR.S33105

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2


Carla Vaz Ferreira, Débora Rodrigues Siqueira, Lucieli Ceolin, Ana Luiza Maia

Thyroid Section, Endocrine Division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

Abstract: Medullary thyroid carcinoma (MTC) is a rare malignant tumor originating from thyroid parafollicular C cells. This tumor accounts for 3%–4% of thyroid gland neoplasias. MTC may occur sporadically or be inherited. Hereditary MTC appears as part of the multiple endocrine neoplasia syndrome type 2A or 2B, or familial medullary thyroid cancer. Germ-line mutations of the RET proto-oncogene cause hereditary forms of cancer, whereas somatic mutations can be present in sporadic forms of the disease. The RET gene encodes a receptor tyrosine kinase involved in the activation of intracellular signaling pathways leading to proliferation, growth, differentiation, migration, and survival. Nowadays, early diagnosis of MTC followed by total thyroidectomy offers the only possibility of cure. Based on the knowledge of the pathogenic mechanisms of MTC, new drugs have been developed in an attempt to control metastatic disease. Of these, small-molecule tyrosine kinase inhibitors represent one of the most promising agents for MTC treatment, and clinical trials have shown encouraging results. Hopefully, the cumulative knowledge about the targets of action of these drugs and about the tyrosine kinase inhibitor-associated side effects will help in choosing the best therapeutic approach to enhance their benefits.

Keywords: medullary thyroid carcinoma, proto-oncogene RET, tyrosine kinase inhibitors

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