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An Exploration into the Origins and Pathogenesis of Anaplastic Large Cell Lymphoma, Anaplastic Lymphoma Kinase (ALK)-Positive
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Cancers 2017, 9(11), 148; https://doi.org/10.3390/cancers9110148

Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers

1
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Almedinah, Medina P.O. Box 41477, Saudi Arabia
2
Department of Laboratory Medicin and Pathology, University of Alberta, Edmonton, AB T6G 2E1, Canada
Received: 26 August 2017 / Revised: 29 September 2017 / Accepted: 24 October 2017 / Published: 28 October 2017
(This article belongs to the Special Issue Targeting ALK in Cancer)
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Abstract

Targeting anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially identified as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) in the form of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors has shown to be a promising therapeutic approach for ALK-expressing tumors. However, clinical resistance to ALK inhibitors invariably occurs, and the molecular mechanisms are incompletely understood. Recent studies have clearly shown that clinical resistance to ALK inhibitors is a multifactorial and complex mechanism. While few of the mechanisms of clinical resistance to ALK inhibitors such as gene mutation are well known, there are others that are not well covered. In this review, the molecular mechanisms of cancer stem cells in mediating resistance to ALK inhibitors as well as the current understanding of the molecular challenges in targeting ALK in ALK-expressing human cancers will be discussed. View Full-Text
Keywords: anaplastic lymphoma kinase; ALK-expressing cancers; cancer stem cells; crizotinib; clinical resistance; tyrosine kinases; tyrosine kinase inhibitors anaplastic lymphoma kinase; ALK-expressing cancers; cancer stem cells; crizotinib; clinical resistance; tyrosine kinases; tyrosine kinase inhibitors
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Alshareef, A. Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers. Cancers 2017, 9, 148.

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