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

Abdulraheem Alshareef

doi:10.3390/cancers9110148

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

Cancers (Basel). 2017 Oct 28;9(11):148. doi: 10.3390/cancers9110148.

Author

Abdulraheem Alshareef^{1

2}

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Almedinah, Medina P.O. Box 41477, Saudi Arabia. amshareef@taibahu.edu.sa.
² Department of Laboratory Medicin and Pathology, University of Alberta, Edmonton, AB T6G 2E1, Canada. amshareef@taibahu.edu.sa.

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.

Keywords: ALK-expressing cancers; anaplastic lymphoma kinase; cancer stem cells; clinical resistance; crizotinib; tyrosine kinase inhibitors; tyrosine kinases.

Publication types

Review