Cyclooxygenas ben deregulated the identification of genes in the main lines

In combination with IL-2 or IFN and Thymosin 1 lead to progression-free survival of a few weeks or a few months with different marginal response rates. Therefore, the most effective treatment of melanoma are urgently n Necessary, which ben deregulated the identification of genes in the main lines Term, the amplifier Gives ndnis the mechanisms drug resistance, and the Cyclooxygenas discovery of some m Chtiger pharmacological agents and delivery systems for these drugs . The deregulation of the mitogen-activated protein kinase in many human cancers, confinement Together Lich melanoma, h Frequently due to mutations in the RAS-RAF and B genes or other genetic or epigenetic events. In melanoma, the mutation rate for RAF B 50 to 70% and is concerning NRAS Gt 15 to 30%. KRAS and HRAS are mutated in 2 and 1% of patients.
Constitutive activation of the MAPK pathway regulates key processes such as cell proliferation, Indirubin survival invasion metastasis, and angiogenesis, which is in the development of melanoma. Although the MAPK is Haupts Chlich activated by mutations in Ras and Raf B if B melanoma RAF or RAS mutations signal cascade by other mechanisms, including normal autocrine MET loan C on the expression of St is a receptor factor hepatocyte or by regulating the low inhibitory proteins as MAPK pathway inhibitor protein an RAF SPRY or 2. In tumors with an inactive B RAF proteins, mutated RAS or C RAF activate MAPK cascade induces the growth of melanoma and drug resistance.
This review provides an insight into the therapeutic potential of targeting the MAPK pathway, the r Of the functional kinases in this signaling cascade, the clinical benefit of pharmacological agents targeting key members of this pathway Played and latest developments in system administration of a therapeutic agent, with an emphasis on encapsulation and drug nanoliposomal siRNA targeting the MAP kinase pathway. 2.0. overview of the MAPK pathway and potential therapeutic targets of the MAPK pathway is classical RAS, RAF, MEK and ERK, relay proliferative signals sequentially surface receptors at the cell surface generated and cytoplasmic signaling in the nucleus. In normal cells, the signaling pathway by binding of mitogens, hormones, neurotransmitters and receptor tyrosine kinases, which are obtained by dimerization to foreign St oncogenic RAS activation Hen stimulates cellular level RAS GTP.
Mechanically, the phosphorylated SH2 domain of Grb2 brings the adapter protein SOS N He inactivity t membrane localized GDP-bound RAS and converts it into an active GTP bound RAS. Activated RAS l st Then the formation of the complex with MAPK downstream Rts RAF MEK1 / 2, ERK 1/2 and a plurality of scaffolding proteins Initiate the cascade MAPK and PI3K potentiates AKT signaling. The active protein RAF triggering Sen dissociation of ERK1 / 2 complex MAPK by phosphorylation, which regulates the expression of several genes in the cell proliferation, differentiation and survival of involved phosphorylation of nuclear transcription factors such as ETS ELK 1 MYC or indirectly intracellular targeted re signaling molecules such as p90 RSK. MAPK phosphorylation also affects the translation by apoptotic regulatory molecular