Clinical trials of agents was In these classes show different activity T toxicity and t can on the pharmacology of the individual drugs and tumor-specific molecular profile of patients. Pharmacodynamic studies suggest that.80% inhibition of ERK for activity.56 Clinical adverse events were required rash, fatigue, nausea and diarrhea. Specific side effects go Most important of these from BMS-387032 keratoacanthoma skin or epidermal carcinoma With specific inhibitors of BRAF, and retinal toxicity t with MEK inhibitors. Laboratory results indicate that it can be feedback loops in the system of the biological and clinical relevance of the activity of MAPK and genotype t Determining of specific agents. For example, the development of BPD and b Associated sartigen skin tumors such as keratoacanthomas and squamous cell carcinomas with BRAF inhibitors, probably due to the paradoxical MAPK occur in wild-type cells BRAF.
57 Clinical studies show that inhibition of RAF wild type leads to upregulation of RAS signaling and activation of ERK. Furthermore, the results of three studies that inhibitors selective for mutant BRAF can CRAF through the formation of complexes RAF dimers activate a process BIBW2992 by the presence of an oncogene RAS is mutation.58 61 These studies improved thought conclusion that mutated BRAF specific inhibitors incurred for the treatment of cancer with mutated BRAF, should be used, but should not be used as monotherapy in melanoma with RAS mutations, because they f tumorigenesis rdern can k. Such a mechanistic view of the MAPK pathway in normal and disease agents and suggest that some combinations can k Preferable in some contexts, molecular and lead the development of effective new therapies for cancer.
Selective mutant BRAF inhibitor vemurafenib vemurafenib is an inhibitor of a mutated form of the BRAF kinase and the second agent for ipilimumab for OS in patients with advanced melanoma.15 improve Phase III called BRIM 3, previously untreated patients with advanced melanoma who received V600E mutation randomized either vemurafenib or dacarbazine get housed. Observed a significant improvement in OS was 6 months in the vemurafenib group, compared to dacarbazine group. In the interim analysis of OS and the Lockable end analysis of progression-free survival was vemurafenib with a significant reduction of 63% compared to the risk of death and 74% risk of death or disease progression of associated reports dacarbazine.
H INDICATIVE side effects associated with vemurafenib were arthralgia, rash, fatigue, hair loss, sensitivity to light, nausea and diarrhea. Epidermal carcinoma Developed with skin, keratoacanthoma, or both in 18% of patients. All versions L Were treated by simple excision. This is the first study to show that a rational actor were aimed at improving the aberrant survival by inhibiting hyperactive signaling pathway in melanoma. Resistance to vemurafenib Despite the benefits associated with vemurafenib, both intrinsic and acquired resistance was observed in patients with advanced melanoma seen. New evidence schl gt before, That resistance is complex and multifactorial vemurafenib.