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Am J Manag Care. 2022 Jan;28(2 Suppl):S15-S25. doi: 10.37765/ajmc.2022.88834.
The tropomyosin receptor kinase (TRK) family of proteins is encoded by neurotrophic tyrosine receptor kinase (NTRK) genes and has a role in the development and normal functioning of the nervous system. NTRK gene fusions have been identified as oncogenic drivers in a wide range of tumors in both adult and pediatric patients. There has recently been a paradigm shift in cancer treatment toward biomarker-based targeted therapies, as an increasing number of actionable targets are being identified across different tumors and/or tumor histologies. These targeted agents offer greater comparative effectiveness and safety vs historical nontargeted standard therapies. The development of drugs that specifically target oncogenic drivers of cancer has led to the emergence of screening technologies to identify the patients most likely to benefit from targeted therapy. This review describes the role of NTRK gene fusions in cancer and outlines the epidemiology of NTRK gene fusions, the therapeutic benefits of targeting TRK fusions with small molecule inhibitors, and recommendations for NTRK gene fusion testing in adult and pediatric patients with cancer, in order to guide treatment decisions.
原肌球蛋白受体激酶 (TRK) 蛋白家族由神经营养酪氨酸受体激酶 (NTRK) 基因编码，在神经系统的发育和正常功能中发挥作用。NTRK 基因融合已被确定为成年和儿科患者多种肿瘤的致癌驱动因素。癌症治疗最近发生了从基于生物标志物的靶向治疗的范式转变，因为越来越多的可操作靶点在不同的肿瘤和/或肿瘤组织学中被识别。与历史上的非靶向标准治疗相比，这些靶向药物具有更高的疗效和安全性。专门针对癌症致癌驱动因素的药物的开发导致了筛选技术的出现，以确定最有可能从靶向治疗中受益的患者。本文描述了 NTRK 基因融合在癌症中的作用，并概述了 NTRK 基因融合的流行病学、用小分子抑制剂靶向 TRK 融合的治疗益处，以及对成人和儿科癌症患者进行 NTRK 基因融合检测的建议，以指导治疗决策。
