at diNt form of brain tumor. Most of the patients at diagnosis with advanced grade 4 tumors. Prim Re glioblastomas show h Fair Gain Gain EGFR tyrosine kinase receptor and secondary Glioblastomas Ren Ren, on the processing of low-grade tumors and less hours Ufigen EGFR h verst RKT 3-Methyladenine occur. EGFR abnormalities from an important r glioblastoma therapies that EGFR have been tested extensively in this disease. EGFR signals through a complex network of intermediate confinement, Lich mitogenactivated PI3K, Akt, protein kinase C and phospholipase ?. MTOR is an important target of EGFR, linking the abundance of growth factor for growth and cell reproduction. Pathways linking EGFR, PI3K, Akt and mTOR kinases downstream Rts with U re in various cancers, mainly due to the mutation of the gene independently the tumor suppressor PTEN activation Embroidered ngig of PI3K and hard drives act Ngig RESISTANCE EGFR and best way to order the upstream inhibition of EGFR give Rtigen. Particularly with the EGFR oncogene involved as in the implementation of malignant gliomas, it was expected that the inhibition of the EGFR signaling is an effective therapeutic strategy. First results with EGFR inhibitors in glioblastoma Uschend were however dice U, which do not respond to most patients. Only patients showing activated verst RKT EGFR mutation and wild-type PTEN short term responses to EGFR inhibitors. However, these patients are only a minority of patients with glioblastoma.
What is the is large number of patients with EGFR-driven tumors, PTEN mutations, which do not respond to treatment for EGFR inhibitor clouds Sup with the apparent activity t of mutant ABT-492 EGFR inhibitors against EGFR engine Ltigen PTEN glioma, we have continued the signaling between EGFR, Akt, mTOR, and glioma cell lines and primary tumors analyzed derived Re glioma patients. Here is the best term we mTOR pa robust marker for the antiproliferative activity of t T of EGFR inhibitors. In contrast, Akt activity Well tt with the antiproliferative effects of EGFR blockade correlated. It is shown that the inhibition of EGFR by mTOR, which depends on the protein kinase C h And hangs Ngig independent-Dependent Akt, downstream signals PKC Rts PTEN in glioma signaling and proliferation of PKC inhibitors block glioma independent Ngig acting ngig state PTEN and EGFR. These studies suggest, dass An important link between PKC signaling and mTOR and EGFR respond as a therapeutic target in malignant gliomas results glioma EGFR wild-type PTEN usually a blockade of EGFR, w During EGFR-mutant glioma conducted no PTEN . In line with these observations, we found that treatment of cell lines with EGFR inhibitor erlotinib PTENwt led to his arrest in G1, w W During treatment PTENmt similar lines had little effect. The amount of EGF p act in the treated cells showed a dose – dependent-dependent reduction in all cell lines,