Dataset Information

MET in glioma: signaling pathways and targeted therapies.

ABSTRACT: Gliomas represent the most common type of malignant brain tumor, among which, glioblastoma remains a clinical challenge with limited treatment options and dismal prognosis. It has been shown that the dysregulated receptor tyrosine kinase (RTK, including EGFR, MET, PDGFR?, ect.) signaling pathways have pivotal roles in the progression of gliomas, especially glioblastoma. Increasing evidence suggests that expression levels of the RTK MET and its specific stimulatory factors are significantly increased in glioblastomas compared to those in normal brain tissues, whereas some negative regulators are found to be downregulated. Mutations in MET, as well as the dysregulation of other regulators of cross-talk with MET signaling pathways, have also been identified. MET and its ligand hepatocyte growth factor (HGF) play a critical role in the proliferation, survival, migration, invasion, angiogenesis, stem cell characteristics, and therapeutic resistance and recurrence of glioblastomas. Therefore, combined targeted therapy for this pathway and associated molecules could be a novel and attractive strategy for the treatment of human glioblastoma. In this review, we highlight progress made in the understanding of MET signaling in glioma and advances in therapies targeting HGF/MET molecules for glioma patients in recent years, in addition to studies on the expression and mutation status of MET.

SUBMITTER: Cheng F

PROVIDER: S-EPMC6585013 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MET in glioma: signaling pathways and targeted therapies.

Cheng Fangling F Guo Dongsheng D

Journal of experimental & clinical cancer research : CR 20190620 1

Gliomas represent the most common type of malignant brain tumor, among which, glioblastoma remains a clinical challenge with limited treatment options and dismal prognosis. It has been shown that the dysregulated receptor tyrosine kinase (RTK, including EGFR, MET, PDGFRα, ect.) signaling pathways have pivotal roles in the progression of gliomas, especially glioblastoma. Increasing evidence suggests that expression levels of the RTK MET and its specific stimulatory factors are significantly incre ...[more]

PMID: 31221203

Similar Datasets

Project description:IntroductionNumerous therapeutic agents specifically targeting the mesenchymal-epithelial transition (MET) oncogene are being developed.ObjectiveThe aim of the current review was to systematically identify and analyze clinical trials that have evaluated MET inhibitors in various cancer types and to provide an overview of their clinical outcomes.MethodsAn electronic literature search was carried out in the PubMed and Embase databases to identify published clinical trials related to MET inhibitors. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement was followed for the systematic appraisal of the literature. Data related to clinical outcomes, including progression-free survival, overall survival, objective response rate, and overall tumor response, were extracted.ResultsIn total, 49 publications were included. Among these, 51.02% were phase II studies, 14.28% were randomized controlled trials, three were phase III studies, two were prospective observational studies, and the remainder were either phase I or Ib studies. The majority (44.89%) of articles reported the clinical outcomes of MET inhibitors, including small molecules, monoclonal antibodies, and other agents, in patients with non-small-cell lung cancer (NSCLC) harboring MET alterations. MET amplification, overexpression, and MET exon 14 skipping mutations were the major MET alteration types reported across the included studies. Clinical responses/outcomes varied considerably.ConclusionThis systematic literature review provides an overview of the literature available in Embase and PubMed regarding MET-targeted therapies. MET-selective tyrosine kinase inhibitors (TKIs) (capmatinib, tepotinib, and savolitinib) may become a new standard of care in NSCLC, specifically with MET exon 14 skipping mutations. A combination of MET TKIs with epidermal growth factor receptor (EGFR) TKIs (osimertinib + savolitinib, tepotinib + gefitinib) may be a potential solution for MET-driven EGFR TKI resistance. Further, MET alteration (MET amplification/overexpression) may be an actionable target in gastric cancer and papillary renal cell carcinoma.

Dataset Information

MET in glioma: signaling pathways and targeted therapies.

Publications

MET in glioma: signaling pathways and targeted therapies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets