Rearranged during transfection (RET) is involved in the physiological development of some organ systems. Activating RET alterations via either gene fusions or point mutations are potent oncogenic drivers in non-small cell lung cancer, thyroid cancer, and in multiple diverse cancers. RET-altered cancers were initially treated with multikinase inhibitors (MKIs). The efficacy of MKIs was modest at the expense of notable toxicities from their off-target activity. Recently, highly potent and RET-specific inhibitors selpercatinib and pralsetinib were successfully translated to the clinic and FDA approved. We summarize the current state-of-the-art therapeutics with preclinical and clinical insights of these novel RET inhibitors, acquired resistance mechanisms, and future outlooks.

转染期间重排（RET）参与某些器官系统的生理发育。通过基因融合或点突变激活RET改变是非小细胞肺癌、甲状腺癌和多种癌症的有效致癌驱动因素。RET改变的癌症最初用多激酶抑制剂 (MKI) 治疗。MKI 的功效有限，但代价是其脱靶活性产生了显着的毒性。最近，强效RET特异性抑制剂selpercatinib和pralsetinib成功转化为临床并获得FDA批准。我们总结了当前最先进的治疗方法，包括这些新型 RET 抑制剂的临床前和临床见解、获得性耐药机制和未来展望。