Mullally W J, O'Leary C G, O'Byrne K J
Department of Medical Oncology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
Department of Medical Oncology, Mater Misericordiae Hospital, South Brisbane, Queensland 4101, Australia.
Lung Cancer. 2025 Feb;200:108083. doi: 10.1016/j.lungcan.2025.108083. Epub 2025 Jan 17.
The enhanced comprehension of the molecular pathways underpinning oncogenesis in non-small cell lung cancer (NSCLC) has led to the advancement of personalized treatment for individuals with actionable mutations using targeted therapies. The rearranged during transfection (RET) proto-oncogene, is critical in the embryonic development of various tissues, including renal, neural, and neuroendocrine tissue. RET fusions have been observed in approximately 1-2% of NSCLC cases. Targeted therapies for NSCLC with RET alterations have progressed significantly over the past decade. While multikinase inhibitors (MKIs) faced limitations in efficacy and tolerability, the introduction of selective RET inhibitors (SRIs) such as selpercatininb and pralsetinib has transformed patient outcomes, resulting in deep and durable responses. Ongoing clinical trials are exploring their potential benefits in the neoadjuvant and adjuvant setting. Early phase clinical trials endeavor to demonstrate next-generation selective RET inhibitors can effectively overcome SRI resistance mechanisms, offer improved safety profiles, and enhance patient outcomes.
对非小细胞肺癌（NSCLC）致癌作用分子途径的深入理解，推动了针对具有可操作突变个体采用靶向疗法进行个性化治疗的发展。转染重排（RET）原癌基因在包括肾脏、神经和神经内分泌组织在内的各种组织的胚胎发育中起关键作用。在约1%-2%的NSCLC病例中观察到RET融合。在过去十年中，针对具有RET改变的NSCLC的靶向治疗取得了显著进展。虽然多激酶抑制剂（MKIs）在疗效和耐受性方面存在局限性，但选择性RET抑制剂（SRIs）如塞尔帕替尼和普拉替尼的引入改变了患者的治疗结果，产生了深度且持久的反应。正在进行的临床试验正在探索它们在新辅助和辅助治疗中的潜在益处。早期临床试验致力于证明下一代选择性RET抑制剂能够有效克服SRI耐药机制，提供更好的安全性，并改善患者治疗结果。
