Tian Zhichao, Niu Xiaohui, Yao Weitao
Department of Orthopedics, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.
Department of Orthopedic Oncology, Beijing Jishuitan Hospital, Beijing, China.
Front Oncol. 2020 Aug 28;10:1642. doi: 10.3389/fonc.2020.01642. eCollection 2020.
Recent clinical trials have shown several multi-target tyrosine kinase inhibitors (TKIs) to be effective in the treatment of osteosarcoma. However, these TKIs have a number of targets, and it is yet unclear which of these targets has a key role in osteosarcoma treatment. In this review, we first summarize the TKIs that were studied in clinical trials registered on ClinicalTrials.gov. Further, we compare and discuss the targets of these TKIs. We found that TKIs with promising therapeutic effect for osteosarcoma include apatinib, cabozantinib, lenvatinib, regorafenib, and sorafenib. The key targets for osteosarcoma treatment may include VEGFRs and RET. The receptor tyrosine kinases (RTKs) MET, IGF-1R, AXL, PDGFRs, KIT, and FGFRs might be relevant but unimportant targets for osteosarcoma treatment. Inhibition of one type of RTK for the treatment of osteosarcoma is not effective. It is necessary to inhibit several relevant RTKs simultaneously to achieve a breakthrough in osteosarcoma treatment. This review provides comprehensive information on TKI targets relevant in osteosarcoma treatment, and it will be useful for further research in this field.
近期临床试验表明，几种多靶点酪氨酸激酶抑制剂（TKIs）在骨肉瘤治疗中有效。然而，这些TKIs有多个靶点，目前尚不清楚其中哪个靶点在骨肉瘤治疗中起关键作用。在本综述中，我们首先总结了在ClinicalTrials.gov上注册的临床试验中研究的TKIs。此外，我们比较并讨论了这些TKIs的靶点。我们发现，对骨肉瘤具有潜在治疗效果的TKIs包括阿帕替尼、卡博替尼、乐伐替尼、瑞戈非尼和索拉非尼。骨肉瘤治疗的关键靶点可能包括血管内皮生长因子受体（VEGFRs）和重组人源化表皮生长因子受体（RET）。受体酪氨酸激酶（RTKs）中的间质表皮转化因子（MET）、胰岛素样生长因子-1受体（IGF-1R）、AXL受体酪氨酸激酶（AXL）、血小板衍生生长因子受体（PDGFRs）、干细胞生长因子受体（KIT）和成纤维细胞生长因子受体（FGFRs）可能是骨肉瘤治疗相关但不重要的靶点。抑制一种类型的RTK治疗骨肉瘤无效。有必要同时抑制几种相关的RTK，以在骨肉瘤治疗上取得突破。本综述提供了骨肉瘤治疗中相关TKI靶点的全面信息，将有助于该领域的进一步研究。
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