医学
肺癌
融合基因
化疗
癌症研究
肿瘤科
靶向治疗
内科学
癌症
基因
生物
遗传学
作者
Hui Jing Hoe,Benjamin Solomon
出处
期刊:Cancer
[Wiley]
日期:2025-03-15
卷期号:131 (S1)
摘要
Aberrant activation of the RET oncogene by mutations or gene fusions drives various malignancies, including 1%-2% of all non-small cell lung cancers (NSCLCs) that harbor RET gene fusions. Initial attempts to target RET fusion-positive NSCLC with poorly selective multikinase RET inhibitors were associated with significant toxicities and limited efficacy. Two highly potent and selective RET small-molecule inhibitors, selpercatinib and pralsetinib, were granted accelerated approval for advanced RET fusion-positive NSCLC by the US Food and Drug Administration, and have been shown to be highly effective both in treatment-naive and previously treated patients with NSCLC. Selpercatinib has shown superiority over chemotherapy in a phase 3 study (LIBRETTO-431) in previously untreated patients with RET fusion-positive NSCLC, which established its place as the standard of care in this patient population. This review discusses the biology and clinical characteristics of RET-rearranged NSCLC and summarizes the evolution of treatment strategies, current understanding of mechanisms of resistance, and development of new-generation agents to overcome resistance.
科研通智能强力驱动
Strongly Powered by AbleSci AI