Discovery of Bcl-3 inhibitors for the potential treatment of metastatic breast cancer

Although treatment options have improved recently for some types of breast cancer (e.g. ductal carcinoma in situ), the prognosis for invasive/metastatic forms of the disease remains poor. One particularly problematic form of breast cancer (15-25% of UK cases) is known as HER2 (ErbB2) positive disease, and is associated with invasive and metastatic disease. Recent developments in HER2 positive breast cancer therapy, including Herceptin, have had limited impact in this disease and are frequently associated with resistant disease.
Pilot studies have established a protein known as Bcl-3 as an exciting new HER2-positive breast cancer target. Bcl-3 leads to metastasis of HER2- positive mammary tumours without compromising normal mammary function. In addition, in vivo deletion of the Bcl-3 gene resulted in a dramatic reduction in metastatic lung tumours with no significant effect on primary mammary tumour growth. We have used computer modelling of the Bcl-3 protein to identify potential candidate molecules for subsequent chemical synthesis and anticancer evaluation. This project builds on and extends these pilot studies to bring together expertise in Bcl-3 biology, computational drug design and medicinal chemistry to develop novel and selective Bcl-3 inhibitor drug candidates with the potential to improve the treatment of invasive breast cancer.
We seek a highly motivated, well-organised student capable of working and thrive in a multidisciplinary research environment. The successful candidate should possess, or expect to obtain an MSc degree or 1st Class BSc degree or equivalent in Medicinal Chemistry or relevant subject area. As the candidate will be also involved in some of the biological aspects of the project (performing ELISA and cell-based assays), any experience in this field would be also desirable. Excellent literacy, numeracy and IT skills are required.