apoptosis Lich F input F promotion from growth and proliferation Ment suppress. It is important that inhibitors of activated mTORC1 by PI3K signaling. The t is the efficiency of mTOR blockade t Co Out Length behavior of other pipes L Akt signaling pathways and length. Contribution to the overall results Uschend die Watching us with mTOR inhibitors Clinical Stops blockade PI3K and mTOR and mTOR combined also suppresses the activation of PI3K with mTOR inhibitors observed in monotherapy. We recently this approach by combining two inhibitors rapamycin mTOR inhibitor, PIK 90 with an inhibitor of PI3K, was also tested, and a dual inhibitor of PI3K and mTOR was well tolerated validated LY2157299 Possible and effective against glioma xenografts. This article examines clinical pr support the use of combination therapies against EGFR and PI3K in glioma and collimated shown that PI3K inhibitors with mTOR inhibitors in this disease as well. The goal of our current EGFR inhibitors work should be tested in combination with a dual inhibitor of PI3K and mTOR in glioma. In this paper we show that the IP 103 mutant cooperate with erlotinib in PTEN mutant glioma in establishing a mechanistic justification for blocking EGFR, PI3K, mTOR and PTEN glioma EGFRdriven treatment. For small r PTEN Ren as a determinant of response to EGFR inhibitors mTOR signaling PI3K, we transduced EGFR in glioma cell lines LN229 and U87, and erlotinib or PI 103rd Unlike cell line U87 PTENmt: EGFR, LN229: EGFR cells showed a significant response to erlotinib.
Analysis by flow cytometry showed G0G1 arrest in LN229 cells. In contrast, U87: EGFR cells showed modest. These data are consistent with the results of other than PTEN status is an important determinant of the response to EGFR inhibitors. Mutations in PTEN should not st with the PI3K signaling pathways coupling mTOR Ren, we found that PTEN status may be less important for the 103rd dual inhibitor of PI According to this model PI 103 was also effective against cells PTENwt and PTENmt. The arrest in G0G1 response to this compound, in contrast to the dependence Dependence dependence A66 Dependence PTEN clearly observed using erlotinib, suggesting that PTEN status PI not a determinant of response to the dual PI3K and mTOR inhibitor 103rd See downstream targets, the response of the cells to EGFR glioma we block immune cells in the K Body and in response PTENwt convey use phospho Antique PTENmt erlotinib. Treatment of cells with EGF resulted in reactions corresponds MAPkinases PTEN signaling Ngig independently Ngig of their status, as indicated by the levels of Erk p. Inhibition of EGFR affects the levels of the same p Erk family there in both cell lines, in accordance with the EGFR signaling pathways to connect MAP kinases are adversely by PTEN status Chtigt. However, even if the treatment with activated EGF