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Giving AXL the axe: targeting AXL in human malignancy

The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic...

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Detalles Bibliográficos
Autores principales: Gay, Carl M, Balaji, Kavitha, Byers, Lauren Averett
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318970/
https://www.ncbi.nlm.nih.gov/pubmed/28072762
http://dx.doi.org/10.1038/bjc.2016.428
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author Gay, Carl M
Balaji, Kavitha
Byers, Lauren Averett
author_facet Gay, Carl M
Balaji, Kavitha
Byers, Lauren Averett
author_sort Gay, Carl M
collection PubMed
description The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation.
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spelling pubmed-53189702017-02-27 Giving AXL the axe: targeting AXL in human malignancy Gay, Carl M Balaji, Kavitha Byers, Lauren Averett Br J Cancer Review The receptor tyrosine kinase AXL, activated by a complex interaction between its ligand growth arrest-specific protein 6 and phosphatidylserine, regulates various vital cellular processes, including proliferation, survival, motility, and immunologic response. Although not implicated as an oncogenic driver itself, AXL, a member of the TYRO3, AXL, and MERTK family of receptor tyrosine kinases, is overexpressed in several haematologic and solid malignancies, including acute myeloid leukaemia, non-small cell lung cancer, gastric and colorectal adenocarcinomas, and breast and prostate cancers. In the context of malignancy, evidence suggests that AXL overexpression drives wide-ranging processes, including epithelial to mesenchymal transition, tumour angiogenesis, resistance to chemotherapeutic and targeted agents, and decreased antitumor immune response. As a result, AXL is an attractive candidate not only as a prognostic biomarker in malignancy but also as a target for anticancer therapies. Several AXL inhibitors are currently in preclinical and clinical development. This article reviews the structure, regulation, and function of AXL; the role of AXL in the tumour microenvironment; the development of AXL as a therapeutic target; and areas of ongoing and future investigation. Nature Publishing Group 2017-02-14 2017-01-10 /pmc/articles/PMC5318970/ /pubmed/28072762 http://dx.doi.org/10.1038/bjc.2016.428 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under the Creative Commons Attribution-Non-Commercial-Share Alike 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/
spellingShingle Review
Gay, Carl M
Balaji, Kavitha
Byers, Lauren Averett
Giving AXL the axe: targeting AXL in human malignancy
title Giving AXL the axe: targeting AXL in human malignancy
title_full Giving AXL the axe: targeting AXL in human malignancy
title_fullStr Giving AXL the axe: targeting AXL in human malignancy
title_full_unstemmed Giving AXL the axe: targeting AXL in human malignancy
title_short Giving AXL the axe: targeting AXL in human malignancy
title_sort giving axl the axe: targeting axl in human malignancy
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5318970/
https://www.ncbi.nlm.nih.gov/pubmed/28072762
http://dx.doi.org/10.1038/bjc.2016.428
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