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AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma

AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemosta...

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Autores principales: Yan, Siyang, Vandewalle, Niels, De Beule, Nathan, Faict, Sylvia, Maes, Ken, De Bruyne, Elke, Menu, Eline, Vanderkerken, Karin, De Veirman, Kim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896070/
https://www.ncbi.nlm.nih.gov/pubmed/31694201
http://dx.doi.org/10.3390/cancers11111727
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author Yan, Siyang
Vandewalle, Niels
De Beule, Nathan
Faict, Sylvia
Maes, Ken
De Bruyne, Elke
Menu, Eline
Vanderkerken, Karin
De Veirman, Kim
author_facet Yan, Siyang
Vandewalle, Niels
De Beule, Nathan
Faict, Sylvia
Maes, Ken
De Bruyne, Elke
Menu, Eline
Vanderkerken, Karin
De Veirman, Kim
author_sort Yan, Siyang
collection PubMed
description AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly diverse, not only between the different tumor types but also in the surrounding tumor microenvironment. Most research and clinical evidence has been provided for AXL inhibitors in acute myeloid leukemia. However, recent studies also revealed an important role of AXL in lymphoid leukemia, lymphoma, and multiple myeloma. In this review, we summarize the basic functions of AXL in various cell types and the role of AXL in different hematological cancers, with a focus on AXL in the dormancy of multiple myeloma. In addition, we provide an update on the most promising AXL inhibitors currently in preclinical/clinical evaluation and discuss future perspectives in this emerging field.
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spelling pubmed-68960702019-12-23 AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma Yan, Siyang Vandewalle, Niels De Beule, Nathan Faict, Sylvia Maes, Ken De Bruyne, Elke Menu, Eline Vanderkerken, Karin De Veirman, Kim Cancers (Basel) Review AXL belongs to the TAM (TYRO3, AXL, and MERTK) receptor family, a unique subfamily of the receptor tyrosine kinases. Their common ligand is growth arrest-specific protein 6 (GAS6). The GAS6/TAM signaling pathway regulates many important cell processes and plays an essential role in immunity, hemostasis, and erythropoiesis. In cancer, AXL overexpression and activation has been associated with cell proliferation, chemotherapy resistance, tumor angiogenesis, invasion, and metastasis; and has been correlated with a poor prognosis. In hematological malignancies, the expression and function of AXL is highly diverse, not only between the different tumor types but also in the surrounding tumor microenvironment. Most research and clinical evidence has been provided for AXL inhibitors in acute myeloid leukemia. However, recent studies also revealed an important role of AXL in lymphoid leukemia, lymphoma, and multiple myeloma. In this review, we summarize the basic functions of AXL in various cell types and the role of AXL in different hematological cancers, with a focus on AXL in the dormancy of multiple myeloma. In addition, we provide an update on the most promising AXL inhibitors currently in preclinical/clinical evaluation and discuss future perspectives in this emerging field. MDPI 2019-11-05 /pmc/articles/PMC6896070/ /pubmed/31694201 http://dx.doi.org/10.3390/cancers11111727 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Yan, Siyang
Vandewalle, Niels
De Beule, Nathan
Faict, Sylvia
Maes, Ken
De Bruyne, Elke
Menu, Eline
Vanderkerken, Karin
De Veirman, Kim
AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title_full AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title_fullStr AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title_full_unstemmed AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title_short AXL Receptor Tyrosine Kinase as a Therapeutic Target in Hematological Malignancies: Focus on Multiple Myeloma
title_sort axl receptor tyrosine kinase as a therapeutic target in hematological malignancies: focus on multiple myeloma
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896070/
https://www.ncbi.nlm.nih.gov/pubmed/31694201
http://dx.doi.org/10.3390/cancers11111727
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