With in the parameters of the first and second line showed no improvement in response rate, progression-free survival, or OS.74, 75 Currently, clinical trials of the combination of sorafenib with other targeted concentrated immunomodulator and chemotherapeutics. RAF265 RAF265 is also an inhibitor of multi-target AZD1152-HQPA molecule from the small and VEGFR mutant BRAF V600E. A Phase I treatment of patients with advanced melanoma RAF265 showed a response rate of 16% for BRAF mutation positive melanoma patients and 13% for the wild-type BRAF mutation status or unknown because of patients.76 In the dose-limiting toxicity Dermatological th an intermittent schedule will be examined in order to improve the therapeutic index.
That this agent provides Cediranib a particular advantage of more selective and potent inhibitors of BRAF, vemurafenib and GSK2118436 as in future clinical trials to be determined. MEK MEK inhibitors is an attractive therapeutic target because it is both active behind BRAF and NRAS. Preclinical studies have suggested that melanoma cell lines sensitive to mutated BRAF lifted towards MEK than inhibiting harboring activating mutations RNA and wild-type BRAF genes.77 small molecule inhibitors of tumor growth are completely Constantly MEK BRAF mutant xenografts, w were you during RAS mutated tumors only partially entered inhibited.77 agents, the clinical development of 1040, PD 0325901, GSK1120212 and AZD6244 IC go ren. The activity of t The first and second generation MEK inhibitor CI-1040 and PD 0325901 was on pharmacological and toxicity Limited t.
Cl 1040 was an officer who was well tolerated in general but not demonstrated sufficient Antikrebsaktivit t to justify further development. 78 PD 0325901 is structurally Similar to Cl 1040, but it is more potent inhibition of MEK and gr Ere systemic exposure. In phase I studies, patients with melanoma phosphorylated specimens.78 objective response and suppression of ERK in melanoma, 79 However, the clinical development stopped due to the high incidence of muscle and neurological contingencies. New MEK inhibitors as GSK1120212 seem to have more power and have shown promising clinical activity of t, Especially for tumors with BRAF mutations. GSK1120212 is a reversible inhibitor GSK1120212, selective allosteric both MEK1 and MEK2. Preclinical studies have shown that inhibiting the phosphorylation of ERK and had growth inhibition in various cancer cell lines lines.
80 The first phase of the human phase I GSK212 concerning the recommended dose Gt 2 to determine daily.81Common II toxicity Th grade were 1 mg and 2 skin rash and diarrhea. There were three F Lle of reversible central water Sen retinopathy. Seventy-two of 162 patients included in the study had advanced melanoma. Among the 24 melanoma patients had tumors hosted BRAF mutations, 24 a wild type BRAF, and 22 had BRAF unknown status. There were two CRs and six PRs among the 20 evaluable patients with BRAF mutant melanoma for a preliminary ruling objective response rate of 40%. In contrast, two of the 22 evaluable patients with wild-type BRAF melanoma PR. These results suggest that the response is correlated with BRAF mutation status.