Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer
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
© 2013 The Author(s). This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.