Kurzfassung

The mTOR pathway is activated in Bcr-Abl-positive cells and has been shown to be crucial for cellular proliferation and survival. Therefore, a combination of targeted therapies using Imatinib plus a mTOR-inhibitor (RAD001) is an attractive and novel approach to potentially overcome subclinical and clinical resistance to imatinib in CML. In this project, the in-vitro effects of Imatinib, RAD001 and a combination of other small molecule inhibitors on proliferation and induction of apoptosis...The mTOR pathway is activated in Bcr-Abl-positive cells and has been shown to be crucial for cellular proliferation and survival. Therefore, a combination of targeted therapies using Imatinib plus a mTOR-inhibitor (RAD001) is an attractive and novel approach to potentially overcome subclinical and clinical resistance to imatinib in CML. In this project, the in-vitro effects of Imatinib, RAD001 and a combination of other small molecule inhibitors on proliferation and induction of apoptosis using Bcr-Abl positive cell lines and primary human CML cells is being evaluated. In addition, the effects of imatinib, RAD001 and a combination of small molecule inhibitors on biomarkers of the Bcr-Abl pathway (tyrosine phosphorylation of STAT5 etc.) and on the mTOR pathway (pS6 etc) will be investigated by novel techniques. These assays are also being used to monitor the above mentioned biomarkers within a clinical trial using a combination of RAD001 and Imatinib in imatinib-resistant CML.» weiterlesen» einklappen