Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110004, China.
Wuya College of Innovation, School of Pharmacy, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
Biomed Pharmacother. 2022 Jun;150:112974. doi: 10.1016/j.biopha.2022.112974. Epub 2022 Apr 18.
Clinical practice shows that when single-target drugs treat multi-factor diseases such as tumors, cardiovascular system and endocrine system diseases, it is often difficult to achieve good therapeutic effects, and even serious adverse reactions may occur. Multi-target drugs can simultaneously regulate multiple links of disease, improve efficacy, reduce adverse reactions, and improve drug resistance. They are ideal drugs for treating complex diseases, and therefore have become the main direction of drug development. At present, some multi-target drugs have been successfully used in many major diseases. Entrectinib is an oral small molecule inhibitor that targets TRK, ROS1, and ALK. It is used to treat locally advanced or metastatic solid tumors with NTRK1/2/3, ROS1 and ALK gene fusion mutations. It can pass through the blood-brain barrier and is the only TRK inhibitor clinically proven to be effective against primary and metastatic brain diseases. In 2019, entrectinib was approved by the FDA to treat adult patients with ROS1-positive metastatic non-small cell lung cancer. Case reports showed that continuous administration of entrectinib was effective and tolerable. In this review, we give a brief introduction to TKK, ROS1 and ALK, and on this basis, we give a detailed and comprehensive introduction to the mechanism of action, pharmacokinetics, pharmacodynamics, clinical efficacy, tolerability and drug interactions of entrectinib.
临床实践表明，当单靶点药物治疗肿瘤、心血管系统和内分泌系统等多因素疾病时，往往难以达到良好的治疗效果，甚至可能出现严重的不良反应。多靶点药物可以同时调节疾病的多个环节，提高疗效，降低不良反应，提高耐药性，是治疗复杂疾病的理想药物，因此成为药物研发的主要方向。目前，一些多靶点药物已成功应用于多种重大疾病。恩曲替尼是一种针对 TRK、ROS1 和 ALK 的口服小分子抑制剂，用于治疗具有 NTRK1/2/3、ROS1 和 ALK 基因融合突变的局部晚期或转移性实体瘤。它可以穿透血脑屏障，是唯一经临床证实对原发性和转移性脑疾病有效的 TRK 抑制剂。2019 年，恩曲替尼被 FDA 批准用于治疗 ROS1 阳性转移性非小细胞肺癌的成人患者。病例报告显示，连续给予恩曲替尼有效且耐受良好。在这篇综述中，我们简要介绍了 TKK、ROS1 和 ALK，并在此基础上详细全面地介绍了恩曲替尼的作用机制、药代动力学、药效学、临床疗效、耐受性和药物相互作用。
