The receptor-tyrosine kinase RET has been identified as a potentially actionable driver of oncogenesis. Several multikinase inhibitors with activity against RET have been explored in the clinic, but have only modest efficacy in patients with thyroid cancers, mostly in those with RET mutations, or RET-rearranged lung cancers. Herein, the authors outline the aberrations in RET that contribute to tumorigenesis, review the current clinical data for inhibitors of this kinase, and discuss whether the limited clinical success achieved with these agents to date is attributable to the intractability of RET as a drug target or the lack of highly specific RET inhibitors.

受体酪氨酸激酶RET已被鉴定为可能的致癌作用驱动因子。临床上已经探索了几种具有抗RET活性的多激酶抑制剂，但对甲状腺癌患者仅具有中等的疗效，主要是在患有甲状腺癌的患者中。RET 突变，或 RET重排的肺癌。在此，作者概述了导致肿瘤发生的RET畸变，回顾了该激酶抑制剂的最新临床数据，并讨论了迄今为止这些药物取得的有限临床成功是否归因于RET作为药物靶标的难治性或缺乏高度特异性的RET抑制剂。