Ricciuti Biagio, Brambilla Marta, Metro Giulio, Baglivo Sara, Matocci Roberta, Pirro Matteo, Chiari Rita
Department of Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Via Dottori, 1, 06156, Perugia, Italy.
Department of Medicine, University of Perugia, Perugia, Italy.
Med Oncol. 2017 Jun;34(6):105. doi: 10.1007/s12032-017-0967-5. Epub 2017 Apr 25.
In the era of personalized medicine, the identification of targetable genetic alterations represented a major step forward in anticancer therapy. NTRK rearrangements represent the molecular driver of a subset of solid tumors, including 3% of non-small-cell lung cancers (NSCLCs). Preliminary data indicate that molecularly selected NSCLC patients harboring NTRK fusions derive an unprecedented clinical benefit from Trk-directed targeted therapies. The aim of this review is to describe the molecular biology of NTRK signaling pathway and to summarize the preclinical data on novel Trk inhibitors, touching upon the clinical development of these inhibitors for the treatment of advanced NSCLC, which have already shown encouraging anticancer activity and acceptable safety profile in early phase I clinical trials.
在精准医学时代，可靶向性基因改变的鉴定是抗癌治疗向前迈出的重要一步。神经营养酪氨酸激酶受体（NTRK）重排是一部分实体瘤的分子驱动因素，包括3%的非小细胞肺癌（NSCLC）。初步数据表明，经分子筛选出的携带NTRK融合的NSCLC患者从靶向Trk的靶向治疗中获得了前所未有的临床益处。本综述的目的是描述NTRK信号通路的分子生物学，并总结新型Trk抑制剂的临床前数据，同时探讨这些抑制剂用于治疗晚期NSCLC的临床进展，这些抑制剂在I期临床试验早期已显示出令人鼓舞的抗癌活性和可接受的安全性。
