the inThis clinical trial design, it relates with the initial Ispinesib SB-715992 results reported. Despite promises of efficiency due to the toxicity of t such combinations is clearly a concern. Farnesyltransferase Pr Clinical trials have demonstrated the efficacy of farnesyl transferase inhibitors as monotherapy for Lonafarnib cells Bcr Abl positive CML and BCR-ABL-induced leukemia premiums Demonstrated in a mouse model. Lonafarnib also inhibits the proliferation of imatinib-resistant CML cell lines and primary rzellen From imatinib-resistant patients. In addition, some are suggesting in vitro studies that Lonafarnib k can Reduce the number of inactive, perhaps stem cells resistant CML imatinib in combination with imatinib.
In a pilot study recently ver Ffentlicht, has the effi ciency of the RTI in a cohort of patients examined with CML in chronic phase and accelerated 13, who had not imatinib and interferon Alvespimycin ? ?? ? ? herapy. Two patients had a h Dermatological reaction temporarily. Lonafarnib has also been associated with imatinib in a phase I study with 22 patients who did not study in combination imatinib. over 30 of the patients achieved a h hematological remission. K promoter hypermethylation hypomethylating agent Can also r In the progression of CML. 5 aza 2 deoxycytidine, a hypomethylating agent was investigated in the LMC. In early clinical studies, this compound as a single agent at a dose of 50 mg to 100 m2 used for 6 hours every 12 hours for 5 days every 4 8 weeks. 55 patients in accelerated phase and blast crisis, 28 patients achieved an h Dermatological reaction.
Because of its immunosuppressive effect, occurring infections in 34 patients, lower doses of decitabine are now preferred. A dose of 15 mg per day for 10 days has been m2. On 35 patients with imatinib failure, 12 and 17 in the chronic phase and accelerated phase Complete h Hematological response in 12 patients was reported, 7 patients had a partial remission dermatological h. In a Phase II study with the same schedule 28 patients were enrolled, 25 with imatinib resistance. Complete h Hematological response was observed at 32. Interestingly, the response rate h Forth in patients without mutations Bcr-Abl kinase Cathedral ne. Other strategies with funds combined imatinib and other drugs are currently under investigation. To go Ren PI3K mTOR inhibitors, bcr abl RNAi, histone deacetylase inhibitors, and others.
Phosphatidylinositol 3-kinase mTOR and its downstream substrate are essential for the survival and proliferation of BCR-ABL transformed cells. MTOR inhibitors rapamycin and RAD001 was shown to inhibit the proliferation of CML cell lines, and it has been shown that rapamycin and imatinib synergistically Bcr Abl transformed cell lines. Regarding the Thr315Ile mutation ConfL icting data on the effects of imatinib and rapamycin have been reported. Mohi et al found these compounds act synergistically in Ph Genotype resistant to imatinib, w While Ly et al and Dengler et al found no effect of imatinib or rapamycin in Bcr Abl Thr315Ile cells positive. The combined treatment of imatinib with mTOR inhibitors may be effective in cases F, Where Bcr Abl mutants do not cause completely’s Full resistance to imatinib. Decreased expression of a target protein kinase c