Breast development and function is influenced by steroid hormones. The initiating events in breast cancer are unknown and cells with genetic changes, which are likely to remain morphologically undetectable for a number of years, will be exposed for an extended period to systemic influences from the endocrine, dietary and metabolic environment.
Breast cancers are comprised of multiple subtypes with the ER and PR (progesterone receptor) used as prognostic and predictive markers in helping define clinically important subgroups of breast cancer. The expression of NRs is associated with breast cancer prognostic factors, treatment resistance and outcomes.
ER+ breast cancers frequently recur after adjuvant treatment and only a small proportion of these advanced cancers will respond subsequently to available treatment options. ER- breast cancers, particularly in younger women, have poorer prognosis and fewer treatment options. These breast cancer subgroups are currently underserved with existing treatment options and new approaches are required to reduce the impact of breast cancer in these subgroups. These breast cancer subgroups are the focus for the NRBC research program.
ER and PR are members of the nuclear receptor superfamily that regulate complex genetic programmes often consisting of thousands of genes, with temporally and spatially regulated expression. As NRs serve as master regulators of virtually every aspect of life, from embryogenesis, through to reproduction, metabolism and cell death, the targeting of NR pathways is now common in diabetes, inflammation, osteoporosis and cardiovascular disease,
Because the components of NR networks are so closely interlinked, their simultaneous evaluation will provide the power required to identify critical players in breast cancer biology. The knowledge gained from the NRBC project will be translated through the application of treatments with existing (NR ligands) regimes in women who have failed on endocrine or cytotoxic treatments. This research program will also provide future scope for new rational small molecule agents to be developed and tested in clinical trials.
