Lower Dovitinib concentrations of ATO k Nnte achievable in vivo. The results of the study Redondo ? al Mu oz and can have significant long-term impact on clinicaltranslational CLL. In addition to the identification and characterization of a mechanism by which ATO surveilance-Dependent inhibition of AKT leads to apoptosis of leukemia Miezellen, they throw the M Possibility of future clinical trials with combinations of ATO with PI 3-K inhibitors. There is currently a great interest in it the orientation of the PI 3-kinase for the treatment of various types of cancer and is rapidly developing means to that end with various pr Clinical and clinical studies course. The results Redondo ? al Mu oz are promising, as the induction of apoptosis betr Chtliches extent of leuk mix cells was observed when the PI 3-K inhibitors were combined with low concentrations of ATO.
There are several PI3 K or double PI-3-kinase mTOR inhibitors WZ4002 currently in phase I K II studies in solid tumors, w During a PI-3-K inhibitor dermatologic currently in Phase I clinical trials in B malignancies, confinement Lich LLC. The results of these clinical trials, it is possible that combinations of ATO with one or more of these agents k Nnte Also be explored in future clinical trials in CLL. A particularly important observation in Redondo ? Mu Oz study was that although arsenic trioxide had a very strong impact on the per-apoptotic cell leukemia Mie, it is very minimal impact on normal blood lymphocytes had peripherals t. This was at final concentrations of arsenic trioxide 3 M.
observed This result suggests a certain specificity of t potential arsenic trioxide to malignant cells as compared to normal cells, although these mechanisms to examine and define accuracy remain in future studies. Future studies should include the effect of arsenic trioxide on the downstream effectors of the mTOR pathway, the PI 3-kinase-Akt activation in leuk mix Cells. Earlier studies have shown that arsenic trioxide obtained paradoxically Hen mTOR activation and engagement of the downstream effectors of mTOR in cells, BCR-ABL and AML cells and combinations of ATO with mTORC1 inhibitor rapamycin lead obtained Hter apoptosis and enhanced suppressive effects on primary re leuk shore cells mix Preferences.
As Arsenic trioxide has suppressive effects on the commitment of the PI3 K AKT in leuk Mix cells, it is likely that it will suppress After all, also found downstream effectors of the mTOR pathway, but it should be examined directly in future studies. Should miezellen M Possible synergy of combinations of ATO with mTOR inhibitors on b Sartigen Leuk Also be considered, especially since it already ongoing efforts to evaluate the clinical effects of mTOR inhibition in the treatment of the LLC. In recent years there has been a renewed interest in the clinical use of arsenic trioxide for the treatment of other h Dermatological malignancy Th beyond APL. Working Redondo Mu