PTEN phosphatase code uses phosphatidylcholine Inositol 3,4,5 triphosphate GSK1363089 Foretinib xl880 and large he substrate. Loss of PTEN function concentration resulting with AKT hyperphosphorylation protect tumor cells from apoptosis. About 60% of primary Ren Colorectal cancer is hyperphosphorylated AKT. Loss of PTEN mutations induced activating mutations of the phosphatidylinositol 3-kinase catalytic alpha polypeptide and activating KRAS / BRAF / MAPK resistance to apoptosis by cetuximab. Patients were treated with WT KRAS tumors with cetuximab on the basis of a plan, the loss of PTEN was associated with an operating system in much shorter connection. About a third of cancer harboring activating somatic mutations in PIK3CA, and it was reported that these mutations pr Diktiven lack of benefits of therapy are antiEGFR.
Further genetic Ver changes, The resistance can to monoclonal Body antiEGFR go An inhibitor of PI3K signaling, coamplification of PAK4 and AKT, the mediators PI3K downstream signaling is Ren, and amplified Rkende IRS2, the activator of an upstream PI3K signaling pathway. 4th Strategies to protect the resistance a number of Ans, The problem of drug resistance were overcome rpern antiEGFR monoclonal And examined. The combination antiEGFR monoclonal Bodies with cytotoxic chemotherapy has been discussed. Erlotinib and gefitinib, two small molecule oral EGFR inhibitors are inactive. The combination of erlotinib with capecitabine and oxaliplatin in patients with previously treated and the combination of gefitinib with FOLFOX were examined in small phase II trials with positive results, but randomized trials with chemotherapy alone as a contr required.
AntiEGFR dual therapy with monoclonal rpern AntiEGFR antiEGFR and TK inhibitors k Can overcome resistance alone. A response rate of 41% was reported for the combination of cetuximab and erlotinib in patients with refractory Rer disease, but it has been limited to patients with KRAS tumors and BRAFWT. EGFR and Vaskul Ren endothelial growth factor have in common multiple signal transduction pathways with pr Clinical data suggest that drug combinations and antiEGFR antiVEGF have synergistic effect. Patients randomized BOND-2 trial of irinotecan and bevacizumab oxaliplatinrefractory disease but had to ¨ ı cetuximab and bevacizumab with or without irinotecan. Response rates, TTP and OS in favor of the triple drug Se treatment, but these results do not stand up to.
Further study of this combination Two subsequent randomized phase III have shown that not improve combinations of monoclonal rpern Bevacizumab plus antiEGFR results and can tats Erh chlich cause Hte toxicity t, independently Ngig of KRAS mutational status. PACCE study evaluated in combination with chemotherapy or oxaliplatin plus bevacizumab irinotecanbased panitumumab. The dual-arm monoclonal antique With increased body Hter toxicity t and significantly shorter PFS in patients with KRAS WT and mutant brought both tumors. Similar results were observed with the combination of cetuximab to therapy with capecitabine, oxaliplatin and bevacizumab in the study CAIRO2. New agents and combinations used to try to overcome the resistance to antiEGFR monoclonal Body.