TY - JOUR
T1 - Targeting oncogenic ALK and MET
T2 - A promising therapeutic strategy for glioblastoma
AU - Wallace, Gerald C.
AU - Dixon-Mah, Yaenette N.
AU - Vandergrift, W. Alex
AU - Ray, Swapan K.
AU - Haar, Catherine P.
AU - Mittendorf, Amber M.
AU - Patel, Sunil J.
AU - Banik, Naren L.
AU - Giglio, Pierre
AU - Das, Arabinda
N1 - Funding Information:
Acknowledgments Completion of this project was made possible by funding from the National Institutes of Health (NIH) and National Institute of Neurological Disorders and Stroke (NINDS): (NS31622, NS-38146, NS-57811, and NS-41088), the State of South Carolina Spinal Cord Injury Research Project (SCSCIRF), VA (1I01BX001262-01A2), Pfizer, Inc., and the Jerry Zucker Fund for Brain Tumor Research of the MUSC Foundation.
PY - 2013/9
Y1 - 2013/9
N2 - 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.
AB - 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.
KW - AKT
KW - ALK
KW - Glioblastoma
KW - MET
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U2 - 10.1007/s11011-013-9401-7
DO - 10.1007/s11011-013-9401-7
M3 - Review article
C2 - 23543207
AN - SCOPUS:84890234199
SN - 0885-7490
VL - 28
SP - 355
EP - 366
JO - Metabolic Brain Disease
JF - Metabolic Brain Disease
IS - 3
ER -