Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glioma is the most common type of adult brain tumor and glioblastoma, its most aggressive form, has a dismal prognosis. Receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR, ERBB2, ERBB3, ERBB4) family, and the vascular endothelial growth factor receptor (VEGFR), play a central role in tumor progression. We investigated the genetic variants of EGFR, ERBB2, VEGFR and their ligands, EGF and VEGF on glioma and glioblastoma risk. In addition, we evaluated the association of genetic variants of a newly discovered family of genes known to interact with EGFR: LRIG2 and LRIG3 with glioma and glioblastoma risk. Methods. We analyzed 191 tag single nucleotide polymorphisms (SNPs) capturing all common genetic variation of EGF, EGFR, ERBB2, LRIG2, LRIG3, VEGF and VEGFR2 genes. Material from four case-control studies with 725 glioma patients (329 of who were glioblastoma patients) and their 1 610 controls was used. Haplotype analyses were conducted using SAS/Genetics software. Results. Fourteen of the SNPs were significantly associated with glioma risk at p< 0.05, and 17 of the SNPs were significantly associated with glioblastoma risk at p< 0.05. In addition, we found that one EGFR haplotype was related to increased glioblastoma risk at p=0.009, Odds Ratio [OR] = 1.67 (95% confidence interval (CI): 1.14, 2.45). The Bonferroni correction made all p-values non-significant. One SNP, rs4947986 next to the intron/exon boundary of exon 7 in EGFR, was validated in an independent data set of 713 glioblastoma and 2 236 controls, [OR] = 1.42 (95% CI: 1.06,1.91). Discussion. Previous studies show that regulation of the EGFR pathway plays a role in glioma progression but the present study is the first to find that certain genotypes of the EGFR gene may be related to glioblastoma risk. Further studies are required to reinvestigate these findings and evaluate the functional significance.
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PMID:A comprehensive study of the association between the EGFR and ERBB2 genes and glioma risk. 2044 91

Leucine-rich repeats and immunoglobulin-like domains (LRIG) 3 gene is mapped to chromosome 12q13.2, a region that is frequently deleted in a subset of glioblastoma multiforme (GBM). It has been reported that perinuclear LRIG3 staining correlated with low WHO grade of glioma and better survival of the patients. However, the relationship between LRIG3 and glioma is not very clear. The purpose of this study is to demonstrate the impacts of LRIG3 on biological characteristics of glioma and its possible mechanisms. We found that transduction of LRIG3 into glioblastoma cells inhibited cell growth in vitro and in vivo, promoted cell apoptosis, and restrained cell invasion and migration. Further studies demonstrated that LRIG3 negatively regulated the epidermal growth factor receptor (EGFR) signaling pathway. Inhibition of EGFR could reduce the effects of LRIG3 knockdown on cell proliferation and EGFR signaling pathway. In conclusion, LRIG3 functions as a tumor suppressor by attenuating EGFR signaling pathway and the restoration of LRIG3 may offer therapeutic potential against malignant gliomas.
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PMID:LRIG3 modulates proliferation, apoptosis and invasion of glioblastoma cells as a potent tumor suppressor. 2570 90

ROS1 protein-tyrosine kinase fusion proteins are expressed in 1-2% of non-small cell lung cancers. The ROS1 fusion partners include CD74, CCDC6, EZR, FIG, KDELR2, LRIG3, MSN, SDC4, SLC34A2, TMEM106B, TMP3, and TPD52L1. Physiological ROS1 is closely related to the ALK, LTK, and insulin receptor protein-tyrosine kinases. ROS1 is a so-called orphan receptor because the identity of its activating ligand, if any, is unknown. The receptor is expressed during development, but little is expressed in adults and its physiological function is unknown. The human ROS1 gene encodes 2347 amino acid residues and ROS1 is the largest protein-tyrosine kinase receptor protein. Unlike the ALK fusion proteins that are activated by the dimerization induced by their amino-terminal portions, the amino-terminal domains of several of its fusion proteins including CD74 apparently lack the ability to induce dimerization so that the mechanism of constitutive protein kinase activation is unknown. Downstream signaling from the ROS1 fusion protein leads to the activation of the Ras/Raf/MEK/ERK1/2 cell proliferation module, the phosphatidyl inositol 3-kinase cell survival pathway, and the Vav3 cell migration pathway. Moreover, several of the ROS1 fusion proteins are implicated in the pathogenesis of a very small proportion of other cancers including glioblastoma, angiosarcoma, and cholangiocarcinoma as well as ovarian, gastric, and colorectal carcinomas. The occurrence of oncogenic ROS1 fusion proteins, particularly in non-small cell lung cancer, has fostered considerable interest in the development of ROS1 inhibitors. Although the percentage of lung cancers driven by ROS1 fusion proteins is low, owing to the large number of new cases of non-small cell lung cancer per year, the number of new cases of ROS1-positive lung cancers is significant and ranges from 2000 to 4000 per year in the United States and 10,000-15,000 worldwide. Crizotinib was the first inhibitor approved by the US Food and Drug Administration for the treatment of ROS1-positive non-small cell lung cancer in 2016. Other drugs that are in clinical trials for the treatment of these lung cancers include ceritinib, cabozantinib, entrectinib, and lorlatinib. Crizotinib forms a complex within the front cleft between the small and large lobes of an active ROS1 protein-kinase domain and it is classified as type I inhibitor.
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PMID:ROS1 protein-tyrosine kinase inhibitors in the treatment of ROS1 fusion protein-driven non-small cell lung cancers. 2846 16