Current PhD Project: The Role of Redox Proteins in the Radiotherapeutic Response of Breast Cancer.
Breast cancer is the most common form of cancer in women with 49,936 cases diagnosed in 2011. Early stage invasive breast cancer patients are commonly treated using breast conserving surgery (BCS) and radiotherapy (R/T). Treatment is often effective but a significant proportion (~10% at 10 years) of individuals will develop local recurrence (LR), indicating a failure of primary therapy. Survival after relapse is poor especially if diagnosed within 2 years after BCS (65% vs 87% 5 year survival). The cytotoxicity of conventional R/T, is primarily mediated via the production of reactive oxygen species (ROS) and free radicals, that leads to increased oxidative stress, lipid and protein peroxidation, DNA damage and cell death. Many studies have shown, in vitro, that modulation of redox homeostasis can alter the response of cancer cells to low LET radiations often used in conventional R/T. There is a need to improve radiotherapeutic response in cancer; one way that this may be achieved is by targeting redox buffering systems to increase radiation efficacy.
We are looking at novel gluthatione system inhibitor and their effects using a variety of in vitro breast cancer models (2D and 3D). Our main aim is to examine the mechanism of action and influence of the novel drugs, in combination with radiation.
The proposed research will give impact in knowledge through the delivery of scientific advances in understanding the influence of alterations of redox homeostasis to radiotherapeutic response. With respect to societal impact, this project may be an initial stepping stone to improve the outcome of radiotherapy for cancer patients. Although the study is currently focussing upon Breast cancer results may be translatable to other tumour types that are commonly treated by R/T, some of which (e.g. pancreatic cancer) have a very poor prognosis. Pancreatic cancer models will be included as the study progresses. The project will also have impact upon those anticancer therapies that also have induction of oxidative stress as a mechanism of action (e.g. various commonly used chemotherapy agents, incl. cis-platinum, anthracyclines etc).