S KIT autophosphorylation and activation of the canals depends le h KIT downstream. Pr Clinical studies show that cells dasatinib k KIT D816V mutation can, which is resistant to imatinib to inhibit. A study of Schittenhelm et al. also shows a m Y-27632 aligned activity against KIT activation loop mutations D816Y D116F and D816V, which is useful for imatinib-resistant GIST. A phase II multicenter trial of the Swiss Group for Clinical Research found Promotes dasatinib is to test the first-line treatment for gastrointestinal stromal tumors. Pharmaceuticals is developing an orally bioavailable by Crenolanib aroG small molecule to the receptor of platelet derived growth factor with potential antineoplastic activity t. Phase I and Phase IB evaluation of their safety reps Opportunity and pharmacokinetics when combined with other drugs and chemotherapy drugs.
Both studies showed reps Promising opportunity with a lot of results. Crenolanib clinical phase II for the treatment of GISTs with PDGFRA mutations widerstandsf Higer to imatinib and sunitinib NVP-TAE684 in May Pazopanib is a small molecule inhibitor of protein tyrosine kinases comprising a plurality of potential antineoplastic activity t. Pazopanib selectively blocks the receptor vascular endothelial growth factor 1, 2, 3, and a receiver singer kit and platelet-derived growth factor, which inhibit angiogenesis in tumors these receptors were linked. Pazopanib is approved by the FDA for the treatment of renal cell carcinoma. He is currently a clinical trial for the treatment of advanced solid tumors, including normal GIST.
Dovitinib is another inhibitor of KIT / PDGFRA and VEGF-inhibitor developed by Novartis. The first Phase I trials are the reps Opportunity and demonstrated in 35 patients. Its activity t against its potential tyrosine kinase activity against other solid tumors such as postulated GIST. The h Ufigsten side effects associated with dovitinib fatigue, nausea, vomiting and diarrhea. A Phase II is on the way to treat the third imitinib / sunitinib-refractory GIST. Sorafenib is a kinase inhibitor that blocks the oral multi-kinase RAF and VEGF receptor 2 and 3, the growth of tumor cells and angiogenesis target. It also blocks PDGFR B, KIT, FLT 3 and RET. Sorafenib was originally approved by the FDA for the treatment of kidney cancer. Sorafenib is in Phase II trials for the treatment of the fourth imatinib, sunitinib, and nilotinib resistant metastatic GIST.
8.2. HSP-90. Heat Shock Protein 90 is a chaperone protein necessary for the correct folding and activation of other cellular ATPdependent Other proteins, especially kinases. Hsp90 interacts with more than 200 proteins, many of these client proteins AKT, BCR ABL, NPM-ALK, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, VEGFR, which are expressed in CML, CLL, lymphoma , AML, non-tumor-small cell lung cancer, breast cancer, prostate cancer and GIST. It has been found that for the growth of cancer cells, the proliferation and survival. They are the new targets for drugs against clinically validated cancer. HSP 90 has an r Crucial role in the maintenance of a plurality of oncogenic pathways and is necessary to maintain the correct folding, stability T and the functionally active conformation of many aberrant oncoproteins. The pharmacological inhibition of HSP90 by smallmolecules destabilized the protein in cancer cells