Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer Discov. 2020 Apr;10(4):498-505. doi: 10.1158/2159-8290.CD-19-1116. Epub 2020 Feb 24.
alterations have been characterized as oncogenic drivers in multiple cancers. The clinical validation of highly selective RET inhibitors demonstrates the utility of specific targeting of aberrantly activated RET in patients with cancers such as medullary thyroid cancer or non-small cell lung cancer. The remarkable responses observed have opened the field of RET-targeted inhibitors. In this review, we seek to focus on the impact of therapeutic RET targeting in cancers. SIGNIFICANCE: Successful clinical translation of selective RET inhibitors is poised to alter the therapeutic landscape of altered cancers. Questions that clearly need to be addressed relate to the ability to maintain long-term inhibition of tumor cell growth, how to prepare for the potential mechanisms of acquired resistance, and the development of next-generation selective RET inhibitors.
改变已被描述为多种癌症中的致癌驱动因素。高度选择性 RET 抑制剂的临床验证证明了在患有甲状腺髓样癌或非小细胞肺癌等癌症的患者中靶向异常激活的 RET 的特异性的实用性。观察到的显著反应开辟了 RET 靶向抑制剂的领域。在这篇综述中，我们试图关注治疗性 RET 靶向在癌症中的影响。意义：选择性 RET 抑制剂的成功临床转化有望改变改变的癌症的治疗格局。显然需要解决的问题涉及维持肿瘤细胞生长的长期抑制能力、如何为潜在的获得性耐药机制做好准备以及开发下一代选择性 RET 抑制剂。
