在过去的十年中，随着分子平台允许对儿科中枢神经系统 (CNS) 肿瘤的基因组图谱进行表征，儿科神经肿瘤学发生了巨大的变化。 NTRK 融合是致癌驱动改变，已在多种肿瘤类型中发现，包括儿童中枢神经系统肿瘤。近年来，NTRK 抑制剂已成为一类有前途的 NTRK 基因融合儿童中枢神经系统肿瘤靶向治疗药物。在复发性儿童中枢神经系统肿瘤中使用拉罗替尼和恩曲替尼已在很大一部分患者中产生了快速而强劲的反应。尽管接近 20% 的患者会出现自发性骨折，但这些药物的耐受性良好。鉴于复发性疾病患者的现有数据，在前期环境中使用 NTRK 抑制剂的临床试验是疗效测试的下一个自然进展，并且许多试验目前正在进行中。为了优化 NTRK 抑制剂的使用并确定最有可能从中受益的 NTRK 融合阳性 CNS 肿瘤患者，仍然需要解决一些挑战。随着这些药物的使用越来越广泛，耐药性将成为一个更加普遍的问题，需要针对这种情况制定策略。本文总结了 NTRK 抑制剂治疗儿童中枢神经系统肿瘤的现状，并讨论了其未来扩大使用的机遇和挑战。© 2024。作者，获得 Springer Nature Switzerland AG 的独家许可。

Over the last decade, as molecular platforms have permitted the characterization of the genomic landscape of pediatric central nervous system (CNS) tumors, pediatric neuro-oncology has dramatically transformed. NTRK fusions are oncogenic driver alterations that have been found in a multitude of tumor types, including pediatric CNS tumors. In recent years, NTRK inhibitors have emerged as a promising class of targeted therapies for pediatric CNS tumors with NTRK gene fusions. The use of larotrectinib and entrectinib in the relapsed setting for pediatric CNS tumors has resulted in rapid and robust responses in an important fraction of patients. These agents are well tolerated, although close to 20% of patients have spontaneous bone fractures. Given the existing data for patients with relapsed disease, clinical trials using NTRK inhibitors in the upfront setting is the next natural progression of efficacy testing and many are currently underway. There are still several challenges that need to be addressed to optimize the use of NTRK inhibitors and identify the patients with NTRK fusion-positive CNS tumors who are most likely to benefit from them. As these agents are more broadly used, resistance will become a more pervasive issue and strategies will need to be determined for this scenario. This article summarizes the current status of NTRK inhibitors for pediatric CNS tumors and discusses the opportunities and challenges of their expanding use in the future.© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.