A new look at the ALK gene in cancer: copy number gain and amplification

Abstract

To date, ALK-rearrangement is a molecular target in several cancers, i.e. NSCLC. The dramatic benefits of crizotinib have prompted research into identifying other possible patients carrying ALK gene alterations with possible clinical significance. The ALK gene is involved not only in several rearrangements but also in other alterations such as amplification. ALK-amplification (ALK-A) is a common genetic event in several cancers, generally associated with poor outcome and more aggressive behaviour. Here we review the role of ALK-A in cancer as a prognostic and predictive biomarker. Furthermore, several critical issues regarding ALK-A in relation to; methods of detection, acquired resistance and ALK second generation inhibitors are analyzed. We conclude that ALK-A could be an intriguing alteration in the context of targeted therapy.

Keywords: ALK- inhibitors; Anaplastic lymphoma kinase; acquired resistance; amplification; copy number gain; crizotinib; fluorescence in situ hybridization.