Targeting oncogenic ALK and MET: A promising therapeutic strategy for glioblastoma

Gerald C. Wallace, Yaenette N. Dixon-Mah, W. Alex Vandergrift, Swapan K. Ray, Catherine P. Haar, Amber M. Mittendorf, Sunil J. Patel, Naren L. Banik, Pierre Giglio, Arabinda Das

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)355-366
Number of pages12
JournalMetabolic Brain Disease
Issue number3
StatePublished - Sep 2013
Externally publishedYes


  • AKT
  • ALK
  • Glioblastoma
  • MET

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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