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AXL激酶作为癌症治疗的新靶点。

AXL kinase as a novel target for cancer therapy.

作者信息

Wu Xiaoliang, Liu Xuewen, Koul Sanjay, Lee Chang Youl, Zhang Zhenfeng, Halmos Balazs

机构信息

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China. Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, NY, USA.

出版信息

Oncotarget. 2014 Oct 30;5(20):9546-63. doi: 10.18632/oncotarget.2542.

Abstract

The AXL receptor tyrosine kinase and its major ligand, GAS6 have been demonstrated to be overexpressed and activated in many human cancers (such as lung, breast, and pancreatic cancer) and have been correlated with poor prognosis, promotion of increased invasiveness/metastasis, the EMT phenotype and drug resistance. Targeting AXL in different model systems with specific small molecule kinase inhibitors or antibodies alone or in combination with other drugs can lead to inactivation of AXL-mediated signaling pathways and can lead to regained drug sensitivity and improved therapeutic efficacy, defining AXL as a promising novel target for cancer therapeutics. This review highlights the data supporting AXL as a novel treatment candidate in a variety of cancers as well as the current status of drug development targeting the AXL/GAS6 axis and future perspectives in this emerging field.

摘要

AXL受体酪氨酸激酶及其主要配体GAS6已被证明在许多人类癌症(如肺癌、乳腺癌和胰腺癌)中过度表达并被激活,且与预后不良、侵袭性/转移性增加、上皮-间质转化(EMT)表型以及耐药性相关。在不同模型系统中单独使用特异性小分子激酶抑制剂或抗体,或与其他药物联合靶向AXL,可导致AXL介导的信号通路失活,并可恢复药物敏感性和提高治疗效果,这将AXL定义为一种有前景的新型癌症治疗靶点。本综述重点介绍了支持AXL作为多种癌症新型治疗候选药物的数据,以及靶向AXL/GAS6轴的药物开发现状和这一新兴领域的未来展望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7b8d/4259419/95b00a5e7dbb/oncotarget-05-9546-g001.jpg

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