Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer.
Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer.
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DOI：
10.2147/ott.s27671
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发表时间：
2013
影响因子：
4
通讯作者：
De Boer RH
中科院分区：
文献类型：
--
作者：
Hart CD;De Boer RH
甲状腺髓样癌是一种罕见的恶性肿瘤，直到最近才有有效的治疗方法。它的特征通常是受体酪氨酸激酶RET（转染期间重排）、VEGFR 2（血管内皮生长因子受体2）和MET（间充质-上皮转化因子）的突变和过表达，这些都是药物开发的有吸引力的靶点。卡博替尼是一种口服生物可利用的酪氨酸激酶抑制剂，可阻断MET、VEGRF 2和RET，并在III期试验中对甲状腺髓样癌显示出相当大的活性，包括在重度预治疗患者中。其血管内皮生长因子和MET抑制的新组合被认为解决了MET逃逸途径，该途径被认为是由单独抑制血管内皮生长因子引起的非持续肿瘤应答的原因。
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.