Anaplastic lymphoma tyrosine kinase oncogene in human cancer: gene aberrations, methods of detection and therapeutic potential

Anaplastic lymphoma tyrosine kinase (ALK) gene could be an attractive oncotarget in human cancers, since it is involved in several genetic alterations resulting in an aberrant activity of the receptor. To date, ALK-rearrangement represents a molecular target for the treatment of ALK-rearranged Non Small Cell Lung Cancer patients, who are highly sensitive to crizotinib, a specific inhibitor. ALK-rearranged patients treated with crizotinib show relevant clinical implications, however several different resistance mechanisms have been identified. Here we review various critical issues related to ALK-targeting therapy, including ALK gene aberrations, methods of detection, mechanism of acquired resistance and second-generation ALK inhibitors.