We investigated the association between expression of EGFR and downstream signaling components and the response of malignant gliomas to erlotinib in a phase I trial of erlotinib administered either alone or with the alkylating agent temozolomide.
We hypothesized that a polymorphism in the 5'-untranslated region of the epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role in the genesis of these malignant gliomas.
We conclude that miR-7 is a potential tumor suppressor in glioblastoma that acts by targeting multiple oncogenes related to the downstream pathway of EGFR and may serve as a novel therapeutic target for malignant gliomas.
We characterized, for the first time, EGFR molecular alterations in Portuguese patients with malignant glioma and identified a subpopulation of patients presenting putative biomarkers for EGFR-based therapies.
To study the relationship between the expression of this aberrant EGFR and cell proliferation, as well as apoptosis in malignant gliomas, we have developed U-87MG cell transfectants that express the aberrant (mutant-type) or normal (wild-type) EGFR.
This early clinical experience indicates that EGFR inhibitors are well tolerated; however, it remains unclear how best to integrate EGFR inhibition into the management of malignant gliomas.
These studies establish that EGFr-mediated signal transduction is important in the maintenance of malignant glioma, and that trans receptor inhibition is a novel way to abrogate abnormal growth of these tumors.
These findings show that the antisense EGFR oligodeoxynucleotide enveloped with Lipofectin has a possibility to become a useful gene therapy against malignant gliomas.
These data identify an elevated frequency of EGFR gene amplification and EGFRvIII mutation in pediatric HGG than previously recognized and show the likely necessity of targeting multiple genetic alterations in the tumors of these children.
These data are in line with those obtained from studies on gliomas of adults and suggest the existence of two different subsets of malignant gliomas also in pediatric brain tumors: one carrying EGFR gene amplification, the other showing p53 mutations.
The important role of aberrant EGFR signaling in the progression of malignant gliomas makes EGFR-targeted therapies of particular interest in this form of cancer.
The epidermal growth factor (EGFR) pathway is frequently activated in glioblastoma but the clinical efficacy of EGFR inhibitors in malignant glioma has been disappointing.
The aim of this study was to extend our observation to high-grade glioma to assess whether EGFR expression pattern is of value in the discrimination of all IG from noninfiltrative glial lesions (NIG), including gliosis, benign tumors, and demyelinating disease.
The epidermal growth factor receptor variant III (EGFRvIII) is a consistent tumor-specific mutation that is widely expressed in MGs and other neoplasms.
The EGFr gene was simultaneously amplified (with arrangements in 12.5% of gliomas) and overexpressed in 53% (9/17) of malignant gliomas, but never in meningiomas.
Taken together, these findings provide us with an insight into LRIG1 function, and we conclude that LRIG1 evolved in gliomas as a rare feedback negative attenuator of EGFR and could offer a novel therapeutic target to treat patients with malignant gliomas.
Similar efficacy was obtained in highly infiltrative, syngeneic glioma models, and intravenously administered hEGFRvIII-CD3 bi-scFv localized to these orthotopic tumors.<b>Conclusions:</b> We have developed a clinically translatable bispecific antibody that redirects human T cells to safely and effectively treat malignant glioma.