title: Targeting oncogenic ALK and MET: a promising therapeutic strategy for glioblastoma.
abstract: Glioblastoma is the most common aggressive, highly glycolytic, and lethal brain tumor. In fact, it is among the most commonly diagnosed lethal malignancies, with thousands of new cases reported in the United States each year. Glioblastoma's lethality is derived from a number of factors including highly active pro-mitotic and pro-metastatic pathways. Two factors increasingly associated with the intracellular signaling and transcriptional machinery required for such changes are anaplastic lymphoma kinase (ALK) and the hepatocyte growth factor receptor (HGFR or, more commonly MET). Both receptors are members of the receptor tyrosine kinase (RTK) family, which has itself gained much attention for its role in modulating mitosis, migration, and survival in cancer cells. ALK was first described as a vital oncogene in lymphoma studies, but it has since been connected to many carcinomas, including non-small cell lung cancer and glioblastoma. As the receptor for HGF, MET has also been highly characterized and regulates numerous developmental and wound healing events which, when upregulated in cancer, can promote tumor progression. The wealth of information gathered over the last 30 years regarding these RTKs suggests three downstream cascades that depend upon activation of STAT3, Ras, and AKT. This review outlines the significance of ALK and MET as they relate to glioblastoma, explores the significance of STAT3, Ras, and AKT downstream of ALK/MET, and touches on the potential for new chemotherapeutics targeting ALK and MET to improve glioblastoma patient prognosis.
authors.affiliation: Department of Neurosciences and MUSC Brain & Spine Tumor Program, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Gerald C
authors.initials: GC
authors.lastname: Wallace
authors.forename: Yaenette N
authors.initials: YN
authors.lastname: Dixon-Mah
authors.forename: W Alex
authors.initials: WA
authors.lastname: Vandergrift
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Ray
authors.forename: Catherine P
authors.initials: CP
authors.lastname: Haar
authors.forename: Amber M
authors.initials: AM
authors.lastname: Mittendorf
authors.forename: Sunil J
authors.initials: SJ
authors.lastname: Patel
authors.forename: Naren L
authors.initials: NL
authors.lastname: Banik
authors.forename: Pierre
authors.initials: P
authors.lastname: Giglio
authors.forename: Arabinda
authors.initials: A
authors.lastname: Das
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt
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