Memorial Sloan Kettering Cancer Center, New York, NY, USA; Weill Cornell Medical College, New York, NY, USA.
Department of Medicine, Thoracic Oncology Program, The University of Chicago, Chicago, IL, USA.
Cancer Treat Rev. 2024 Jun;127:102733. doi: 10.1016/j.ctrv.2024.102733. Epub 2024 Apr 3.
Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are recurrent oncogenic drivers found in a variety of solid tumours, including lung cancer. Several tropomyosin receptor kinase (TRK) inhibitors have been developed to treat tumours with NTRK gene fusions. Larotrectinib and entrectinib are first-generation TRK inhibitors that have demonstrated efficacy in patients with TRK fusion lung cancers. Genomic testing is recommended for all patients with metastatic non-small cell lung cancer for optimal drug therapy selection. Multiple testing methods can be employed to identify NTRK gene fusions in the clinic and each has its own advantages and limitations. Among these assays, RNA-based next-generation sequencing (NGS) can be considered a gold standard for detecting NTRK gene fusions; however, several alternatives with minimally acceptable sensitivity and specificity are also available in areas where widespread access to NGS is unfeasible. This review highlights the importance of testing for NTRK gene fusions in lung cancer, ideally using the gold-standard method of RNA-based NGS, the various assays that are available, and treatment algorithms for patients.
神经酪氨酸受体激酶（NTRK）基因融合是多种实体瘤中常见的致癌驱动基因，包括肺癌。已经开发了几种原肌球蛋白受体激酶（TRK）抑制剂来治疗具有 NTRK 基因融合的肿瘤。拉罗替尼和恩曲替尼是第一代 TRK 抑制剂，已证明在具有 TRK 融合的肺癌患者中有效。建议对所有转移性非小细胞肺癌患者进行基因组检测，以选择最佳的药物治疗。临床上可以采用多种检测方法来鉴定 NTRK 基因融合，每种方法都有其自身的优势和局限性。在这些检测方法中，基于 RNA 的下一代测序（NGS）可以被认为是检测 NTRK 基因融合的金标准；然而，在广泛获得 NGS 不可行的地区，也有一些具有可接受的灵敏度和特异性的替代方法。本文综述了在肺癌中检测 NTRK 基因融合的重要性，理想情况下应使用基于 RNA 的 NGS 这一金标准方法、各种可用的检测方法以及患者的治疗算法。
