title: An update of ALK inhibitors in human clinical trials.
abstract: The proto-oncogenic ALK is a druggable receptor tyrosine kinase for cancer treatment. Two small molecule inhibitors of ALK, crizotinib and ceritinib, have been recently approved for the treatment of metastatic non-small-cell lung cancer, with marked improvement of progression-free survival of patients. Independent case reports also indicate their potential therapeutic activity in other ALK-rearranged cancers. Numerous single-agent and combination therapy trials are ongoing in lung and many other cancers. Results of these trials are greatly anticipated. Here, we summarize our current understanding of ALK signaling, genomic aberrations in cancer and emerging mechanisms of drug resistance. We will also provide a timely review on all ALK inhibitors and their current status of development in clinical settings.
authors.affiliation: Pharmacogenomics & Precision Therapeutics Laboratory, Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: Eason Leong Yin
authors.initials: EL
authors.lastname: Chan
authors.affiliation: Pharmacogenomics & Precision Therapeutics Laboratory, Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: Claudia Ho Yi
authors.initials: CH
authors.lastname: Chin
authors.affiliation: Pharmacogenomics & Precision Therapeutics Laboratory, Department of Pharmacology & Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.|School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
authors.forename: Vivian Wai Yan
authors.initials: VW
authors.lastname: Lui
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077547:Crizotinib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011720:Pyrazoles / Q000627:therapeutic use*; D011725:Pyridines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D013450:Sulfones / Q000627:therapeutic use*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011725:Pyridines; D011743:Pyrimidines; D013450:Sulfones; D000077547:Crizotinib; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C586847:ceritinib
keywords: ALK alterations; ALK inhibitor; resistance to ALK inhibitor