New drug targets for CLL
Chronic lymphocytic leukaemia (CLL) is the most common adult blood cancer in the UK, comprising around 3,200 new diagnoses in the UK per year, and remains incurable. Although the majority of patients initially respond to conventional chemotherapy, all eventually relapse due to the re-emergence of leukaemic cells that evaded initial treatment. It is now appreciated that the leukaemic CLL cells interact with several types of supportive cells within patient lymphoid organs (lymph nodes and bone marrow); these cells provide survival and growth signals to the leukaemic cells, and several studies demonstrate that these associations protect CLL cells from currently-used treatments. We hypothesise that one particular protein called mTor, which is commonly deregulated in other human cancers, plays a central role in regulating key proteins responsible for CLL cell protection, survival and disease progression. Importantly, mTor has recently been linked with the initiation and progression of acute lymphoblastic leukaemia, but the role of this protein in CLL remains unclear. As mTor represents a promising drug target, with inhibitors of this protein currently being tested in clinical trial, it is of critical importance to gain fundamental information about the biological function of this protein. Therefore, utilising powerful experimental approaches to mimic the tumour microenvironmental of the patient lymphoid organs, this proposal aims to elucidate the role of mTor in the initiation and progression of CLL.