AXL kinase as a novel target for cancer therapy

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

doi:10.18632/oncotarget.2542

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AXL kinase as a novel target for cancer therapy

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

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Oncotarget. 2014; 5:9546-9563. https://doi.org/10.18632/oncotarget.2542

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Abstract

Xiaoliang Wu1,*, Xuewen Liu1,2,*, Sanjay Koul2,*, Chang Youl Lee3, Zhenfeng Zhang1, Balazs Halmos2

1Sun 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

2Division of Hematology/Oncology, Herbert Irving Comprehensive Cancer Center, New York Presbyterian Hospital-Columbia University Medical Center, New York, NY, USA

3Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Chuncheon Sacred Heart Hospital Hallym University Medical Center, Chuncheon-si Gangwon-do 200–704 Republic of Korea

*These authors contributed equally to this work

Correspondence to:

Zhenfeng Zhang, e-mail: [email protected]

Balazs Halmos, e-mail: [email protected]

Keywords: AXL, receptor tyrosine kinase, lung cancer, targeted therapy.

Received: July 23, 2014 Accepted: September 29, 2014 Published: October 16, 2014

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.

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Reviews:

AXL kinase as a novel target for cancer therapy

Abstract