Every year, around 55,000 women are diagnosed with breast cancer. It is estimated that 20% of these cases form a sub-type of breast cancer known as triple negative breast cancer (TNBC). This subset is characterized by lack of expression of the estrogen receptor (ER) and the progesterone receptor (PR). Also, TNBC do not display amplification of HER2/neu receptor.
Among the proteins that have been of interest in understanding and treating breast cancer is the STAT3 protein. Although it is constitutively activated in all breast cancer subtypes, it is most often associated with triple negative tumours. STAT3 regulates the transcription of many cancer relevant genes such as c-Myc, cyclin D1, Bcl-xL, Bcl-2 and survivin. STAT3 activation contributes to cell proliferation, apoptosis, angiogenesis, immune response and metastasis in breast cancer as well as the survival of cancer cells. Notably, it is now understood that STAT3 activity correlates with poor treatment outcomes in cancer therapy.
Several studies have shown that blocking STAT3 function results in apoptosis in tumour cells whereas healthy cells were not only able to survive at very lower level of STAT3 but also capable of growing by alternative mechanisms. Therefore, targeting STAT3 is a very attractive approach in the discovery and development of new anti-cancer treatments with less off-target effects. Among the plausible strategies for inhibiting STAT3 activity is the targeting and inhibition of its dimerization, which is essential for its function.
We have developed a novel approach for targeting STAT3 dimerization, and in this project we aim to use this approach to design, synthesise and test new STAT3 dimerization inhibitors that could be developed into new treatments for TNBC.
The project will involve the design and synthesis of small molecules, therefore the ideal candidate would need to have a chemistry background and an interest in drug development.
By working on this project, the student will acquire detailed knowledge of (breast) cancer biology, drug design, synthesis and purification, cell culture, design of biological assays, data analysis including statistics, data interpretation and problem solving. The student will also have the opportunity to present his/her research in our weekly lab meetings and will be encouraged to attend and present his/her research findings in national and international meetings. Also, he/she will be encouraged to attend the various training opportunities offered by the School and University e.g., “presenting research to non-specialists”, “writing abstracts”, “research philosophy and ethics”. Furthermore, the student will have the opportunity to interact with our partner on this project, Tenovus Cancer Care.
HOW TO APPLY
To apply please click the following link: https://www.cardiff.ac.uk/study/postgraduate/research/programmes/programme/pharmacy
In the "Research proposal and Funding" section of your online application, please specify the project title and supervisors of this project and copy the project description in the text box provided.