Department of Oncology, Royal Melbourne Hospital, Victoria, Australia.
Onco Targets Ther. 2013;6:1-7. doi: 10.2147/OTT.S27671. Epub 2013 Jan 3.
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.
甲状腺髓样癌是一种罕见的恶性肿瘤，直到最近才有了一些有效的治疗方法。它通常表现为受体酪氨酸激酶 RET（转染时重排）、VEGFR2（血管内皮生长因子受体 2）和 MET（间质上皮转化因子）的突变和过表达，这使其成为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、VEGFR2 和 RET，在 III 期试验中已显示出在甲状腺髓样癌中的显著活性，包括在经过大量预处理的患者中。其血管内皮生长因子和 MET 抑制的新组合被认为可以解决 MET 逃逸途径，这被认为是导致单独抑制血管内皮生长因子导致肿瘤反应不能持续的原因。
