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RET融合肺癌的靶向治疗:突破与未解决的问题

Targeted Therapy for RET Fusion Lung Cancer: Breakthrough and Unresolved Issue.

作者信息

Takamori Shinkichi, Matsubara Taichi, Haratake Naoki, Toyokawa Gouji, Fujishita Takatoshi, Toyozawa Ryo, Ito Kensaku, Yamaguchi Masafumi, Taguchi Kenichi, Okamoto Tatsuro, Seto Takashi

机构信息

Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Front Oncol. 2021 Aug 23;11:704084. doi: 10.3389/fonc.2021.704084. eCollection 2021.

Abstract

Molecular drugs targeting mutated or rearranged oncogene drivers have become one of the standard recognized treatments in patients with advanced and recurrent non-small cell lung cancer. is located in the long arm of human chromosome 10 and encodes a receptor tyrosine kinase protein, and RET fusion-positive lung adenocarcinoma occurs in 1%-2% of cases. Clinical trials of multikinase inhibitors, including cabozantinib, vandetanib, sorafenib, and lenvatinib, that inhibit RET oncogene activity have shown their antitumor efficacy. Recently, RET inhibitors such as pralsetinib and selpercatinib that are specialized for RET kinase have also been developed, and their efficacy was investigated in previous clinical trials (BLU-667 and LOXO-292). In this review, we summarized the effects and adverse events of multikinase and selective RET inhibitors and the various diagnostic techniques for gene fusion. In the perspective part, we focused on the unsolved issues on treatment for RET fusion-positive lung cancer and future developments.

摘要

针对突变或重排致癌基因驱动因子的分子药物已成为晚期和复发性非小细胞肺癌患者公认的标准治疗方法之一。RET位于人类10号染色体长臂,编码一种受体酪氨酸激酶蛋白,RET融合阳性肺腺癌发生率为1%-2%。包括卡博替尼、凡德他尼、索拉非尼和乐伐替尼在内的抑制RET致癌基因活性的多激酶抑制剂临床试验已显示出其抗肿瘤疗效。最近,还开发了专门针对RET激酶的RET抑制剂,如普拉替尼和塞尔帕替尼,并在先前的临床试验(BLU-667和LOXO-292)中对其疗效进行了研究。在本综述中,我们总结了多激酶和选择性RET抑制剂的作用及不良事件以及RET基因融合的各种诊断技术。在展望部分,我们重点关注了RET融合阳性肺癌治疗中尚未解决的问题及未来发展。

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引用本文的文献

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本文引用的文献

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A Performance Comparison of Commonly Used Assays to Detect RET Fusions.常用检测 RET 融合的方法的性能比较。
Clin Cancer Res. 2021 Mar 1;27(5):1316-1328. doi: 10.1158/1078-0432.CCR-20-3208. Epub 2020 Dec 3.
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State-of-the-Art Strategies for Targeting -Dependent Cancers.靶向依赖型癌症的最新策略。
J Clin Oncol. 2020 Apr 10;38(11):1209-1221. doi: 10.1200/JCO.19.02551. Epub 2020 Feb 21.

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