title: MET and ALK as targets for the treatment of NSCLC.
abstract: Cell proliferation, survival, differentiation, migration and metabolism are some of the fundamental cellular processes tightly controlled by the activity of tyrosine-kinase receptors (RTKs). The aberrant signaling of RTKs contributes to cancer growth and survival and has become important target for therapeutic approaches. Well-characterized kinase molecular target in lung cancer, in particular in non-small cell lung cancer (NSCLC), is the activated epidermal growth factor receptor (EGFR) pathway. More recently, the oncogenic role of other two tyrosine-kinases, the hepatocyte growth factor receptor (MET) and the anaplastic lymphoma kinase (ALK), has been recognized. Many different therapeutic strategies have been investigated with the goal to inhibit these receptors, subsequent downstream signaling cascades and arrest tumor growth. This review will discuss the MET and ALK pathways, the different strategies of their inhibition and the potential approaches to overcome acquired resistance to kinase inhibitors in these two genes.
authors.forename: M
authors.initials: M
authors.lastname: Capelletti
authors.forename: F
authors.initials: F
authors.lastname: Gelsomino
authors.affiliation: Medical Oncology Unit, University Hospital of Parma, Via Gramsci 14, 43100 Parma, Italy. mtiseo@ao.pr.it.
authors.forename: M
authors.initials: M
authors.lastname: Tiseo
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases