骨肉瘤中的受体酪氨酸激酶：2019 年更新。
Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update.
机构信息
Department of Orthopaedic Surgery, Indiana University School of Medicine and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Department of Orthopaedics, University of Chicago Pritzker School of Medicine, Chicago, IL, USA.
出版信息
Adv Exp Med Biol. 2020;1258:141-155. doi: 10.1007/978-3-030-43085-6_9.
The primary conclusions of our 2014 contribution to this series were as follows: Multiple receptor tyrosine kinases (RTKs) likely contribute to aggressive phenotypes in osteosarcoma and, therefore, inhibition of multiple RTKs is likely necessary for successful clinical outcomes. Inhibition of multiple RTKs may also be useful to overcome resistance to inhibitors of individual RTKs as well as resistance to conventional chemotherapies. Different combinations of RTKs are likely important in individual patients. AXL, EPHB2, FGFR2, IGF1R, and RET were identified as promising therapeutic targets by our in vitro phosphoproteomic/siRNA screen of 42 RTKs in the highly metastatic LM7 and 143B human osteosarcoma cell lines. This chapter is intended to provide an update on these topics as well as the large number of osteosarcoma clinical studies of inhibitors of multiple tyrosine kinases (multi-TKIs) that were recently published.
我们在 2014 年为本系列做出的主要结论如下：多种受体酪氨酸激酶（RTKs）可能促成骨肉瘤的侵袭性表型，因此，成功的临床疗效可能需要抑制多种 RTKs。抑制多种 RTKs 也可能有助于克服对单个 RTKs 抑制剂的耐药性以及对传统化疗的耐药性。不同的 RTKs 组合可能对个别患者很重要。通过对高度转移的 LM7 和 143B 人骨肉瘤细胞系中的 42 种 RTKs 进行体外磷酸蛋白质组学/siRNA 筛选，AXL、EPHB2、FGFR2、IGF1R 和 RET 被确定为有前途的治疗靶点。本章旨在提供这些主题以及最近发表的大量多靶点酪氨酸激酶抑制剂（multi-TKIs）的骨肉瘤临床研究的最新进展。
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