Crizotinib is used for the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) that is anaplastic-lymphoma kinase (ALK)-positive as detected by a FDA-approved test.
Mode of Action:
Crizotinib is a tyrosine kinase receptor inhibitor. More specifically, it inhibits anaplastic lymphoma kinase (ALK), hepatocyte growth factor receptor (HGFR, c-MET), and Recepteur d’Origine Nantais (RON). Abnormalities in the ALK gene caused by mutations or translocations may lead to expression of oncogenic fusion proteins. In patients with NSCLC, they have the EML4-ALK gene. Crizotinib inhibits ALK tyrosine kinase which ultimately results in decreased proliferation of cells that carry the genetic mutation and tumour survivability.
Crizotinib is metabolized by CYP3A4 and CYP3A5 in which these enzymes mediates the O-dealkylation of the drug.
FDA labelTimm A, Kolesar JM: Crizotinib for the treatment of non-small-cell lung cancer. Am J Health Syst Pharm. 2013 Jun 1;70(11):943-7. doi: 10.2146/ajhp120261. PubmedForde PM, Rudin CM: Crizotinib in the treatment of non-small-cell lung cancer. Expert Opin Pharmacother. 2012 Jun;13(8):1195-201. doi: 10.1517/14656566.2012.688029. Pubmed
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