Targeting AXL in NSCLC

Aubhishek Zaman,1,2 Trever G Bivona1,2 1Department of Medicine, University of California, San Francisco, CA, USA; 2UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USACorrespondence: Trever G Bivona Email trever.bivona@ucsf.eduAbstract: State-of-the-art can...

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Autores principales:	Zaman A, Bivona TG
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	lung cancer axl targeted therapy drug resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/01e16318a1f14041832b1e2fd09330bd
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spelling	oai:doaj.org-article:01e16318a1f14041832b1e2fd09330bd2021-12-02T16:26:43ZTargeting AXL in NSCLC1179-2728https://doaj.org/article/01e16318a1f14041832b1e2fd09330bd2021-08-01T00:00:00Zhttps://www.dovepress.com/targeting-axl-in-nsclc-peer-reviewed-fulltext-article-LCTThttps://doaj.org/toc/1179-2728Aubhishek Zaman,1,2 Trever G Bivona1,2 1Department of Medicine, University of California, San Francisco, CA, USA; 2UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USACorrespondence: Trever G Bivona Email trever.bivona@ucsf.eduAbstract: State-of-the-art cancer precision medicine approaches involve targeted inactivation of chemically and immunologically addressable vulnerabilities that often yield impressive initial anti-tumor responses in patients. Nonetheless, these responses are overshadowed by therapy resistance that follows. AXL, a receptor tyrosine kinase with bona fide oncogenic capacity, has been associated with the emergence of resistance in an array of cancers with varying pathophysiology and cellular origins, including in non-small-cell lung cancers (NSCLCs). Here in this review, we summarize AXL biology during normal homeostasis, oncogenic development and therapy resistance with a focus on NSCLC. In the context of NSCLC therapy resistance, we delineate AXL’s role in mediating resistance to tyrosine kinase inhibitors (TKIs) deployed against epidermal growth factor receptor (EGFR) as well as other notable oncogenes and to chemotherapeutics. We also discuss the current understanding of AXL’s role in mediating cell-biological variables that function as important modifiers of therapy resistance such as epithelial to mesenchymal transition (EMT), the tumor microenvironment and tumor heterogeneity. We also catalog and discuss a set of effective pharmacologic tools that are emerging to strategically perturb AXL mediated resistance programs in NSCLC. Finally, we enumerate ongoing and future exciting precision medicine approaches targeting AXL as well as challenges in this regard. We highlight that a holistic understanding of AXL biology in NSCLC may allow us to predict and improve targeted therapeutic strategies, such as through polytherapy approaches, potentially against a broad spectrum of NSCLC sub-types to forestall tumor evolution and drug resistance.Keywords: lung cancer, AXL, targeted therapy, drug resistanceZaman ABivona TGDove Medical Pressarticlelung canceraxltargeted therapydrug resistanceNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol Volume 12, Pp 67-79 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	lung cancer axl targeted therapy drug resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	lung cancer axl targeted therapy drug resistance Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Zaman A Bivona TG Targeting AXL in NSCLC
description	Aubhishek Zaman,1,2 Trever G Bivona1,2 1Department of Medicine, University of California, San Francisco, CA, USA; 2UCSF Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA, USACorrespondence: Trever G Bivona Email trever.bivona@ucsf.eduAbstract: State-of-the-art cancer precision medicine approaches involve targeted inactivation of chemically and immunologically addressable vulnerabilities that often yield impressive initial anti-tumor responses in patients. Nonetheless, these responses are overshadowed by therapy resistance that follows. AXL, a receptor tyrosine kinase with bona fide oncogenic capacity, has been associated with the emergence of resistance in an array of cancers with varying pathophysiology and cellular origins, including in non-small-cell lung cancers (NSCLCs). Here in this review, we summarize AXL biology during normal homeostasis, oncogenic development and therapy resistance with a focus on NSCLC. In the context of NSCLC therapy resistance, we delineate AXL’s role in mediating resistance to tyrosine kinase inhibitors (TKIs) deployed against epidermal growth factor receptor (EGFR) as well as other notable oncogenes and to chemotherapeutics. We also discuss the current understanding of AXL’s role in mediating cell-biological variables that function as important modifiers of therapy resistance such as epithelial to mesenchymal transition (EMT), the tumor microenvironment and tumor heterogeneity. We also catalog and discuss a set of effective pharmacologic tools that are emerging to strategically perturb AXL mediated resistance programs in NSCLC. Finally, we enumerate ongoing and future exciting precision medicine approaches targeting AXL as well as challenges in this regard. We highlight that a holistic understanding of AXL biology in NSCLC may allow us to predict and improve targeted therapeutic strategies, such as through polytherapy approaches, potentially against a broad spectrum of NSCLC sub-types to forestall tumor evolution and drug resistance.Keywords: lung cancer, AXL, targeted therapy, drug resistance
format	article
author	Zaman A Bivona TG
author_facet	Zaman A Bivona TG
author_sort	Zaman A
title	Targeting AXL in NSCLC
title_short	Targeting AXL in NSCLC
title_full	Targeting AXL in NSCLC
title_fullStr	Targeting AXL in NSCLC
title_full_unstemmed	Targeting AXL in NSCLC
title_sort	targeting axl in nsclc
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/01e16318a1f14041832b1e2fd09330bd
work_keys_str_mv	AT zamana targetingaxlinnsclc AT bivonatg targetingaxlinnsclc
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Targeting AXL in NSCLC

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