Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer

Thierry Berghmans,1 Myriam Remmelink,2 Ahmad Awada31Clinic of Thoracic Oncology and Department of Intensive Care, Institut Jules Bordet, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2Department of Pathology, H&ocirc;pital Erasme, Universit&eacute; Libre de Bruxell...

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Autores principales:	Berghmans T, Remmelink M, Awada A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/bd7cdb1d05854b19b7235edc51419c23
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spelling	oai:doaj.org-article:bd7cdb1d05854b19b7235edc51419c232021-12-02T01:39:52ZAnaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer1179-2728https://doaj.org/article/bd7cdb1d05854b19b7235edc51419c232012-12-01T00:00:00Zhttp://www.dovepress.com/anaplastic-lymphoma-kinase-alk-inhibitors-for-second-line-therapy-of-n-a11773https://doaj.org/toc/1179-2728Thierry Berghmans,1 Myriam Remmelink,2 Ahmad Awada31Clinic of Thoracic Oncology and Department of Intensive Care, Institut Jules Bordet, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2Department of Pathology, H&ocirc;pital Erasme, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 3Medical Oncology Clinic, Institut Jules Bordet, Universit&eacute; Libre de Bruxelles, Brussels, BelgiumAbstract: Targeted therapies are nowadays a treatment option in metastatic non-small cell lung cancer, for which oncogenic drivers have been identified. The epidermal growth factor-receptor tyrosine kinase inhibitors gefitinib and erlotinib, are the standard of care for patients in whom tumors are presenting with an activating epidermal growth factor-receptor mutation, with new active agents like afatinib reaching clinics in the near future. Other genetic abnormalities have been documented in squamous and non-squamous lung cancer. The EML4&ndash;ALK gene fusion is a rare event, occurring in around 5% of lung cancer, quite exclusively in adenocarcinoma with a predominance of young non/light smokers. Detection of ALK-positive tumors is challenging, as there is no gold-standard technique. Fluorescence in situ hybridization is the method used in prospective trials assessing the activity of crizotinib and is recommended by the American FDA. Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice. Impressive results came from a phase I study and are now confirmed in a large phase II study with response rate of 60%, whatever the number of previous lines of chemotherapy. Other ALK inhibitors are currently in the preclinical phase, and some are showing promising results in early phase I/II studies. This review aims to present the current knowledge on the EML4&ndash;ALK gene fusion, the pitfalls for the pathologist and the clinician in searching this abnormality, and to review the existing literature on ALK inhibitors under development, focusing their role compared to chemotherapy in non-small cell lung cancer patients.Keywords: non-small cell lung cancer, EML4&ndash;ALK, crizotinibBerghmans TRemmelink MAwada ADove Medical PressarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENLung Cancer: Targets and Therapy, Vol 2012, Iss default, Pp 91-99 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Berghmans T Remmelink M Awada A Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
description	Thierry Berghmans,1 Myriam Remmelink,2 Ahmad Awada31Clinic of Thoracic Oncology and Department of Intensive Care, Institut Jules Bordet, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 2Department of Pathology, H&ocirc;pital Erasme, Universit&eacute; Libre de Bruxelles, Brussels, Belgium; 3Medical Oncology Clinic, Institut Jules Bordet, Universit&eacute; Libre de Bruxelles, Brussels, BelgiumAbstract: Targeted therapies are nowadays a treatment option in metastatic non-small cell lung cancer, for which oncogenic drivers have been identified. The epidermal growth factor-receptor tyrosine kinase inhibitors gefitinib and erlotinib, are the standard of care for patients in whom tumors are presenting with an activating epidermal growth factor-receptor mutation, with new active agents like afatinib reaching clinics in the near future. Other genetic abnormalities have been documented in squamous and non-squamous lung cancer. The EML4&ndash;ALK gene fusion is a rare event, occurring in around 5% of lung cancer, quite exclusively in adenocarcinoma with a predominance of young non/light smokers. Detection of ALK-positive tumors is challenging, as there is no gold-standard technique. Fluorescence in situ hybridization is the method used in prospective trials assessing the activity of crizotinib and is recommended by the American FDA. Crizotinib is the first orally active inhibitor of receptor tyrosine kinases, including ALK and ROS1, in clinical practice. Impressive results came from a phase I study and are now confirmed in a large phase II study with response rate of 60%, whatever the number of previous lines of chemotherapy. Other ALK inhibitors are currently in the preclinical phase, and some are showing promising results in early phase I/II studies. This review aims to present the current knowledge on the EML4&ndash;ALK gene fusion, the pitfalls for the pathologist and the clinician in searching this abnormality, and to review the existing literature on ALK inhibitors under development, focusing their role compared to chemotherapy in non-small cell lung cancer patients.Keywords: non-small cell lung cancer, EML4&ndash;ALK, crizotinib
format	article
author	Berghmans T Remmelink M Awada A
author_facet	Berghmans T Remmelink M Awada A
author_sort	Berghmans T
title	Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
title_short	Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
title_full	Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
title_fullStr	Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
title_full_unstemmed	Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer
title_sort	anaplastic lymphoma kinase (alk) inhibitors for second-line therapy of non-small cell lung cancer
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/bd7cdb1d05854b19b7235edc51419c23
work_keys_str_mv	AT berghmanst anaplasticlymphomakinasealkinhibitorsforsecondlinetherapyofnonsmallcelllungcancer AT remmelinkm anaplasticlymphomakinasealkinhibitorsforsecondlinetherapyofnonsmallcelllungcancer AT awadaa anaplasticlymphomakinasealkinhibitorsforsecondlinetherapyofnonsmallcelllungcancer
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Anaplastic lymphoma kinase (ALK) inhibitors for second-line therapy of non-small cell lung cancer

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