Crizotinib--latest champion in the cancer wars?

Three articles in this issue of the Journal report on the therapeutic potential of a new kid on the kinase inhibitor block: crizotinib, an ATP-competitive inhibitor of the anaplastic lymphoma kinase (ALK) receptor tyrosine kinase. Kwak et al.1 summarize a study involving patients with non–small-cell lung cancer who were enrolled in a phase 1 trial, starting in 2008, hot on the heels of a study in which cell lines derived from non–small-cell lung tumors were shown to be sensitive to NVP-TAE6842 and crizotinib (PF-02341066).3,4 From a cohort of 1500 patients with non–small-cell lung cancer, 82 (5.5%) were found to . . .

[1]  Y. Ishikawa,et al.  KIF5B-ALK, a Novel Fusion Oncokinase Identified by an Immunohistochemistry-based Diagnostic System for ALK-positive Lung Cancer , 2009, Clinical Cancer Research.

[2]  A. Iafrate,et al.  Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors. , 2008, Cancer research.

[3]  Young Lim Choi,et al.  EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. , 2010, The New England journal of medicine.

[4]  R. Palmer,et al.  Anaplastic lymphoma kinase: signalling in development and disease , 2009, The Biochemical journal.

[5]  Marc Ladanyi,et al.  Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. , 2010, The New England journal of medicine.

[6]  Andrea Lombardi Borgia,et al.  Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors. , 2010, Biochemistry.

[7]  H. Aburatani,et al.  Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer , 2007, Nature.

[8]  Shinji Yamazaki,et al.  Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma , 2007, Molecular Cancer Therapeutics.

[9]  Peter G. Schultz,et al.  Identification of NVP-TAE684, a potent, selective, and efficacious inhibitor of NPM-ALK , 2007, Proceedings of the National Academy of Sciences.

[10]  A. Ghose,et al.  ALK mutants in the kinase domain exhibit altered kinase activity and differential sensitivity to small molecule ALK inhibitors. , 2009, Biochemistry.

[11]  T. Clackson,et al.  Abstract LB-298: AP26113, a potent ALK inhibitor, overcomes mutations in EML4-ALK that confer resistance to PF-02341066 (PF1066) , 2010 .

[12]  Beatriz Bellosillo,et al.  Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas: identification of a new TFG-ALK(XL) chimeric gene with transforming activity. , 2002, The American journal of pathology.

[13]  Laura A. Sullivan,et al.  Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer , 2007, Cell.

[14]  Glen Spraggon,et al.  Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain. , 2010, The Biochemical journal.

[15]  John M. Maris,et al.  Identification of ALK as a major familial neuroblastoma predisposition gene , 2008, Nature.

[16]  L. Tanoue,et al.  Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer , 2012 .