Clofarabine has been examined within training regimens for AML just before allogeneic stem cell transplant. Inhibitors of FLT3, including lestaurtinib, midostaurin, sorafenib, and the second generation FLT3 TKI AC220, have already been examined as individual agents. Cabozantinib ic50 Clinical responses have been temporary and changing, and it seems that in vivo inhibition of FLT3 highly correlates with reaction to therapy. Tests of FLT3 inhibitors in combination with chemotherapy in the upfront and relapsed controls claim that there is no toxicity, but longterm data on survival isn’t yet available. Results from 126 patients showed non important differences in rates of CR/CRi. Patients were stratified utilizing the European Prognostic Index, and patients with unfavorable possibility disease who received CPX 351 had a significant improvement in OS. Other drugs in growth The Hedgehog signalling pathway is implicated in the pathogenesis and chemotherapy resistance of Skin infection a number of human malignancies. A task for Hedgehog signalling within the self renewal of leukemia stem cells in acute lymphocytic leukemia, chronic myeloid leukemia, 76 multiple myeloma and lymphoma is described. Original information was presented at the 2011 ASH Annual Meeting with the Hedgehog chemical, PF 04449913. The Phase I trial enrolled patients with relapsed or refractory hematologic malignancies. One patient with AML arising from CMML reached a CRi and five other patients with AML had a significant reduction in circulating leukemia cells. 80 Clinical trials of the drug along with other Hedgehog pathway inhibitors are prepared in deubiquitinating enzyme inhibitors the relapsed and up-front settings in AML. As well as Hedgehog signalling, other paths have been implicated in AML including MEK, mTOR/PI3K and WNT/ catenin. Several mTOR inhibitors have been studied as single agents in relapsed/ refractory AML as well as in mixtures with other chemotherapy. For example, results of a Phase II study of the mTOR inhibitor temsirolimus plus clofarabine in relapsed elderly patients with AML were recently described. Fifty three patients received a salvage reinduction with clofarabine 20 mg/m2/day 5 days and temsirolimus 25 mg on days 1, 8 and 15. Patients obtaining CR/CRi could carry on monthly temsirolimus maintenance. Although the rate of CR/CRi was 21-69, lab correlative reports demonstrated that target inhibition was related to higher costs of clinical response. Studies with histone deactylase inhibitors including panobinostat, vorinostat and romidepsin, are ongoing in MDS and AML. The leukemia microenvironment is disrupted by the CXCR4 antagonist plerixafor and it’s hypothesized that inhibition of the CXCR4/ CXCL12 axis may increase sensitivity to chemotherapy.