Evaluating larotrectinib for the treatment of advanced solid tumors harboring an NTRK gene fusion
Evaluating larotrectinib for the treatment of advanced solid tumors harboring an NTRK gene fusion
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DOI：
10.1080/14656566.2021.1876664
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发表时间：
2021-02-11
影响因子：
3.2
通讯作者：
Satolli, Maria Antonietta
中科院分区：
文献类型：
--
作者：
Filippi, Roberto;Depetris, Ilaria;Satolli, Maria Antonietta
前言：NTRK癌基因家族是一些少见的儿童和成人恶性肿瘤的特征，在一小部分常见癌症中也观察到对NTRK癌基因家族的上瘾。抑制它们的蛋白产物Trk激酶被证明是治疗这些肿瘤的一种成功的策略。内容包括：本文综述了Trk激酶家族的选择性抑制剂larotrectinib治疗NTRK融合阳性癌症的临床进展。这篇手稿包括对疗效、安全性、药代动力学和药效学的概述。作者总结了他们对larotrectinib及其未来潜在用途的专家意见。专家意见：Larotrectinib显示出耐受性和高效性，无论原发部位。2018年，拉洛替尼获得美国食品和药物管理局(FDA)的组织不可知性批准，用于治疗含有NTRK融合的实体肿瘤。主要的挑战将是在普通肿瘤人群中实施NTRK融合的筛查，以及将拉洛替尼纳入治疗算法。
Introduction: Characteristic of some rare pediatric and adult malignancies, addiction to the NTRK oncogene family is also observed in a small fraction of common cancers. Inhibition of their protein products, the Trk kinases, proved a successful treatment strategy for these tumors.Areas covered: The current paper reviews the clinical development of larotrectinib, a selective inhibitor of the Trk kinase family, for the treatment of NTRK fusion-positive cancers. The manuscript includes an overview of the efficacy, safety, pharmacokinetics and pharmacodynamics. The authors sum up by providing the reader with their expert opinion on larotrectinib and its potential future use.Expert opinion: Larotrectinib showed tolerability and high efficacy, regardless of the primary site. In 2018, larotrectinib was granted by the Food and Drug Administration a tissue-agnostic approval for the treatment of solid tumors harboring an NTRK fusion. The major challenges will be the implementation of the screening for NTRK fusions in the general oncologic population, and the incorporation of larotrectinib into the therapeutic algorithms.