Tyrosine kinases have a crucial role as key regulators of signaling pathways 
that influence cell differentiation and growth. Dysregulation of tyrosine 
kinase-mediated signaling is understood to be an important oncogenic driver. 
Genetic rearrangements involving the tyrosine kinase anaplastic lymphoma kinase 
(ALK) gene occur in non-small cell lung cancer (NSCLC), anaplastic large cell 
lymphomoas, inflammatory myofibroblastic tumors, and other cancers. Cells with 
abnormal ALK signaling are sensitive to ALK inhibitors such as crizotinib. This 
review will highlight the discovery of the fusion between echinoderm 
microtubule-associated protein-like 4 (EML4) and ALK as an oncogenic driver, 
recognition of other ALK gene rearrangements in NSCLC, and the confirmation that 
crizotinib is an effective treatment for patients with ALK-positive NSCLC. Work 
is underway to further define the role for crizotinib in the treatment of 
ALK-positive lung cancer and other cancers and to investigate the molecular 
mechanisms for resistance to ALK inhibition with crizotinib.