Crizotinib. ALK/Met inhibitor, oncolytic

There are a number of molecular abnormalities that can occur in normal cells to induce a malignant phenotype. Recently, the tyrosine kinase receptor anaplastic lymphoma kinase (ALK) has been shown to have gain of function when partnered with different proteins. As an example, on chromosome 2p, with inversion, there is translocation with generation of fusion protein EML4-ALK in lung cancer. In a phase I trial, EML4-ALK-positive patients were selected to determine the response to a potent, small-molecule tyrosine kinase inhibitor, crizotinib (PF-02341066). Marked durable responses were observed with crizotinib 250 mg p.o. twice a day. Interestingly, crizotinib also has activity against tyrosine-protein kinase Met. We have previously shown that Met can be overexpressed, sometimes mutated, or sometimes amplified in lung cancer. Thus, this review will emphasize the characteristics of crizotinib and detail the clinical experience.