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Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer

Authors Hart CD, De Boer RH

Received 28 September 2012

Accepted for publication 13 November 2012

Published 3 January 2013 Volume 2013:6 Pages 1—7

DOI https://dx.doi.org/10.2147/OTT.S27671

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Christopher D Hart, Richard H De Boer

Department of Oncology, Royal Melbourne Hospital, Victoria, Australia

Abstract: Medullary thyroid cancer is an uncommon malignancy for which until recently little effective treatment existed. It is often characterized by mutation and overexpression of the receptor tyrosine kinases RET (rearranged during transfection), VEGFR2 (vascular endothelial growth factor receptor 2) and MET (mesenchymal-epithelial transition factor), which make attractive targets for drug development. Cabozantinib is an orally bioavailable tyrosine kinase inhibitor which blocks MET, VEGRF2 and RET, and has shown considerable activity in medullary thyroid cancer in a Phase III trial, including in heavily pretreated patients. Its novel combination of vascular endothelial growth factor and MET inhibition is believed to address the MET escape pathway, which is thought to be the cause of nonsustained tumor responses resulting from inhibition of vascular endothelial growth factor alone.

Keywords: EXAM trial, VEGF escape pathways, MET, RET

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