RET 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.

中文翻译：

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靶向 RET 依赖性癌症的进展

RET 改变已被表征为多种癌症的致癌驱动因素。高选择性 RET 抑制剂的临床验证证明了特异性靶向异常激活的 RET 对甲状腺髓样癌或非小细胞肺癌等癌症患者的效用。观察到的显着反应开辟了 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已改变癌症的治疗前景。显然需要解决的问题涉及维持长期抑制肿瘤细胞生长的能力，如何为获得性耐药的潜在机制做好准备，