ALK-rearrangements and testing methods in non-small cell lung cancer: a review
Rodney E. Shackelford1, Moiz Vora1, Kim Mayhall2, and James Cotelingam1
1 LSU Health Shreveport, Department of Pathology, Shreveport, LA, USA
2 Tulane University School of Medicine, New Orleans, LA, USA
Correspondence:
Rodney E. Shackelford, email:
Keywords: Anaplastic lymphoma kinase, non-small cell lung cancer, pulmonary adenocarcinoma, crizotinib
Received: December 15, 2013 Accepted: April 22, 2014 Published: April 22, 2014
Abstract
The anaplastic lymphoma tyrosine kinase (ALK) gene was first described as a driver mutation in anaplastic non-Hodgkin’s lymphoma. Dysregulated ALK expression is now an identified driver mutation in nearly twenty different human malignancies, including 4-9% of non-small cell lung cancers (NSCLC). The tyrosine kinase inhibitor crizotinib is more effective than standard chemotherapeutic agents in treating ALK positive NSCLC, making molecular diagnostic testing for dysregulated ALK expression a necessary step in identifying optimal treatment modalities. Here we review ALK-mediated signal transduction pathways and compare the molecular protocols used to identify dysregulated ALK expression in NSCLC. We also discuss the use of crizotinib and second generation ALK tyrosine kinase inhibitors in the treatment of ALK positive NSCLC, and the known mechanisms of crizotinib resistance in NSCLC.
