Specificity of fibroblast growth growth factor-induced signalling pathways in human tumours – identification of novel therapeutic targets?

Ovarian cancer is difficult to treat – it is often widespread at diagnosis, and treatment is palliative rather than curative. Ovarian cancer patients are primarily treated by chemotherapy, although response is unpredictable, and often limited by the development of drug-resistant disease. There is, therefore, an urgent clinical need to understand how ovarian tumours spread and become drug resistant and to develop better treatments. Many new drugs in development are targeted to “growth factors”, specialised proteins produced by tumours, which promote cell growth. We are interested in fibroblast growth factors (FGFs) – we have shown that the amount of a protein called fibroblast growth factor 1 (FGF1) varies widely, and is increased in more advanced ovarian tumours. We have created novel experimental models with different amounts of FGF1, and shown that the amount of growth factor produced determines whether tumours respond to cisplatin and carboplatin, the chemotherapy drugs most commonly prescribed to ovarian cancer patients. In this project, we will further investigate FGFs and related proteins in ovarian and other common tumours including breast, colorectal and lung cancers. We will identify additional chemotherapy drugs, where tumour growth factors influence response and will investigate whether blocking growth factor production can halt tumour spread and/or influence response to chemotherapy.