AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Chenjing Zhu; Yuquan Wei; Xiawei Wei

doi:10.1186/s12943-019-1090-3

AXL receptor tyrosine kinase as a promising anti-cancer approach: functions, molecular mechanisms and clinical applications

Mol Cancer. 2019 Nov 4;18(1):153. doi: 10.1186/s12943-019-1090-3.

Authors

Chenjing Zhu^{1

2}, Yuquan Wei¹, Xiawei Wei³

Affiliations

¹ Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China.
² Department of Radiation Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, 42 Baiziting, Nanjing, 210009, Jiangsu, China.
³ Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People's Republic of China. xiaweiwei@scu.edu.cn.

Abstract

Molecular targeted therapy for cancer has been a research hotspot for decades. AXL is a member of the TAM family with the high-affinity ligand growth arrest-specific protein 6 (GAS6). The Gas6/AXL signalling pathway is associated with tumour cell growth, metastasis, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance, immune regulation and stem cell maintenance. Different therapeutic agents targeting AXL have been developed, typically including small molecule inhibitors, monoclonal antibodies (mAbs), nucleotide aptamers, soluble receptors, and several natural compounds. In this review, we first provide a comprehensive discussion of the structure, function, regulation, and signalling pathways of AXL. Then, we highlight recent strategies for targeting AXL in the treatment of cancer.AXL-targeted drugs, either as single agents or in combination with conventional chemotherapy or other small molecule inhibitors, are likely to improve the survival of many patients. However, future investigations into AXL molecular signalling networks and robust predictive biomarkers are warranted to select patients who could receive clinical benefit and to avoid potential toxicities.

Keywords: AXL; Cancer; Inhibitor; Receptor tyrosine kinase; Signaling pathway.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Axl Receptor Tyrosine Kinase
Biomarkers, Tumor*
Cell Proliferation / drug effects
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Disease Progression
Gene Expression Regulation, Neoplastic
Humans
Intercellular Signaling Peptides and Proteins / genetics
Intercellular Signaling Peptides and Proteins / metabolism
Molecular Targeted Therapy
Neoplasms / drug therapy
Neoplasms / etiology*
Neoplasms / metabolism*
Neoplasms / pathology
Protein Kinase Inhibitors / pharmacology*
Protein Kinase Inhibitors / therapeutic use
Proto-Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins / metabolism*
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
Receptor Protein-Tyrosine Kinases / genetics
Receptor Protein-Tyrosine Kinases / metabolism*
Signal Transduction / drug effects

Substances

Antineoplastic Agents
Biomarkers, Tumor
Intercellular Signaling Peptides and Proteins
Protein Kinase Inhibitors
Proto-Oncogene Proteins
growth arrest-specific protein 6
Receptor Protein-Tyrosine Kinases
Axl Receptor Tyrosine Kinase
AXL protein, human