Targeted therapy for NSCLC: ALK inhibition

Purpose: The purpose of this review article is to describe the emerging data of ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC.Summary: ALK mutations have been identified in approximately 2.4-13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers. Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. A phase II study demonstrated an overall response rate of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and visual disturbances. Elevations in lever function tests were also reported.Conclusion: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.