Wever, due to poor Ridaforolimus bioavailability and lack of therapeutic efficacy in early clinical trials of this compound has not been tested for clinical applications. Thus, MEK 1/2 promising therapeutic targets in the MAP kinase pathway. However, better agents or delivery systems to more specific problems, the toxicity t Reduce related ben CONFIRMS. 2.8. Inhibit ERK target for immunohistochemical studies using antique Rpern detected melanoma ERK1 / 2 and phosphorylated ERK were on formalin-fixed sections 42 melanoma, 38 and 20 metastases, nevi performed. ERK1 / 2 was expressed found in varying degrees, in all F Cases in the range of 40% to 100%, and observed in the cytoplasm and nucleus. Only small amounts of ERK1 / 2 were recognized in normal skin melanocytes.
Patients with metastatic melanoma showed h Here pERK subcutaneous metastases compared with metastases in the lymph nodes or N Vu connection. pERK was not in melanocytes, the detected in the normal skin. N RAS and RAF B mutations are h More commonly in the skin or Limonin soft tissue melanoma metastases, the Ren partially explained K Nnte, the differences in the H Perk see in the subcutaneous metastases and lymph node metastases. It was a non-significant relationship between the depth of the melanoma pERK expression. H Heren percentage of positive cells per ERK have nodular melanoma compared with n Vi mild and surface- Chlich spreading melanoma reported. Thus, ERK activation is directly related to the stage of the disease associated with gr Erer activity t in more advanced melanomas.
Currently MEK1 / 2 inhibitor is used as inhibitors of the downstream Rtigen effector of ERK1 / 2 and MEK1 / 2 is known to activate ERK1 / 2 selectively. High ERK activity Is t h Frequently observed for the proliferation of metastatic melanoma cell lines and in human tumors and is a good indicator for tumor progression. Delay Gerter activation of ERK in melanoma cells was shown to confer the best Resistance to various therapeutic agents. Growth factors k Can activate ERK in melanoma, either through the traditional route or a path that is coupled to G-protein coupled receptors. ERK activity in melanocytes can t also be stimulated by mitogens such as bFGF and endothelin first However, the contribution of Ma determined on each channel of the global stimulation of ERK in melanoma.
Activated ERK regulates the expression of splice Variations MITF, MITF 6a / b, and embroidered on the survival of melanoma cells, differentiation, proliferation and migration. Although ERK activity has t Shown that high cell proliferation ligand, under certain circumstances, Inhibit the activation of ERK by cell cycle by regulating p53 expression in place and p16INK4a. Sun ERK has the potential to be an important goal in melanoma. 2.9. Work aims ERK in melanoma Studies using experimental models of metastasis have shown that targeting of ERK1 / 2 is effectively reduced by using siRNA development of lung metastases and sensitized tumor cells to chemotherapeutic agents such as cisplatin. Similar to the low pERK1 / 2 levels are werereported patients with RAF inhibitors sorafenib and B indicates PLX4032 treated pERK1 / 2 is a reasonable biomarker of tumor progression and evaluate the effectiveness of therapeutic agents. Contrary to popular belief, i