Background: Triple negative breast cancers (TNBCs) do not express oestrogen receptors (ERs), progesterone receptors (PRs) or human epidermal growth factor receptor 2 (HER2) on routine immunohistochemical (IHC) analysis. TNBCs account for 10-17% of all breast cancer subtypes, are poorly differentiated and clinically aggressive. To date, there is no tailored therapy for these women due to the lack of any immediately identifiable therapeutic target. As a result, TNBCs are managed with standard chemotherapy such as Taxol®. Consequently, local and systemic relapses are high due to de novo and acquired resistance. We have identified a novel pathway that is important in cell survival that may aid triple negative cancer cells resist chemotherapy. In this project we will test if this pathway is important in human triple negative breast cancers. We will also investigate using pre-clinical studies if inhibiting this pathway will restore tumour sensitivity to drug treatment.
Aims: To investigate (a) the expression of novel pathway proteins using immunohistochemistry (IHC) in a cohort of 200 triple negative formalin fixed paraffin embedded (FFPE) breast tumours (b) correlate resultant protein expression with patient outcome and chemo-responsiveness and (c) to investigate the role of novel pathway proteins and their interaction in mediating Taxol® resistance in TNBC cell lines in vitro.
Impact: Defining the role of novel pathway proteins and their contribution to chemoresistance in TNBC holds great potential for the development of novel drugs that restore chemosensitivity (i.e. small molecules that prevent the biologically significant interaction between these proteins) for women presenting with TNBC.
