This iniM Ge be the m Matched results Questions pharmacology of individual agents, and the lack of inhibition of the target tumor in problems due to non-target or target-specific toxicity Tsgrenze doses. Perifosine Perifosine is an inhibitor of PI3K and AKT and structurally related to miltefosine. St it Rt the recruitment of proteins with pleckstrin Homologiedom PLX-4720 Ne how AKT to the plasma membrane. A phase II study of perifosine in patients treatment was performed with previously untreated metastatic melanoma and 14 evaluable patients achieved an objective no response.86 The extent the inhibition of AKT and MAPK has not been evaluated in this study. The authors recommend that no further development of perifosine alone was necessary for patients with metastatic melanoma.
GSK2141795 is a reversible inhibitor GSK2141795, all selective ATPcompetitive Akt isoforms. Preclinical studies have shown that GSK795 could inhibit the proliferation of cancer cells. A Phase I study with GSK795 was carried out to the recommended dose of Phase Canertinib II, the pharmacokinetics, pharmacodynamics and safety of the drug determine 0.87 Overall, 76 patients were included. In the 54 patients evaluable for response was a PR in a patient with metastatic anal cancer, two patients with endometrial cancer l Ngeren stable disease and smaller tumor responses in the Bev POPULATION for molecularly defined weight Hlt observed pr Diktiven signatures. No response was observed in patients with melanoma, although some were included in this study. Inactivation of mTOR inhibitors PTEN mutations were identified in 50% of melanomas.
88 Erh Hte mTOR activity t is expected that the embroidered normal N Hrstoffe to ��berm what Owned cell growth and derail proliferation.89 However, the results the first clinical trials of the test phase, mTOR inhibitors and derivatives of rapamycin, temsirolimus and everolimus in patients with melanoma also showed a lack of exercise alone. Temsirolimus Temsirolimus is an inhibitor of mTOR kinase intravenous Se ester derivative of rapamycin. When FK506 binding protein is bound, interacts and inhibits mTOR kinase activity t, resulting in inhibition of cell could cycle.90 pr Clinical studies demonstrated that temsirolimus tumor activity t In a plurality of inhibit cancers confinement Lich melanoma cell lines and animal models. A Phase II trial of temsirolimus in patients with metastatic melanoma.
91 thirty-three patients were treated with a single patient with a PR of 2 months, performed. The median time to disease progression was 10 weeks. It is interesting that the dose / schedule used in this study, not the maximum tolerable Possible dose and target inhibition of tumor has not been investigated in this study. Whether anti-tumor activity of t Gr He re w With h Heren doses is an unanswered question. Everolimus Everolimus is an mTOR inhibitor orally. A two-stage phase II study in 29 patients with metastatic melanoma.92 the first vorl INDICATIVE analysis performed, the activity t of everolimus with 35% of patients with SD 16 weeks seemed favorable. The median PFS and OS a little more than 3 months and 12 months.