Breast cancer is the most common form of cancer affecting a large population of women worldwide. Chemotherapy has been the most effective form of treatment against breast cancer. In the majority of patients this is highly impeded by resistance of cancer cells to chemotherapeutic drugs. This project aims to structurally determine BCRP a protein that is responsible for drug resistance in several types of cancer, including breast and brain cancer.

The human Breast Cancer Resistance Protein (BCRP) is a drug efflux pump responsible for conferring drug resistance to many chemotherapeutic agents used for breast cancer treatment. Overexpression of BCRP is associated with high levels of resistance to a variety of anticancer agents used in breast cancer treatment, including anthracyclines, mitoxantrone, and the camptothecins. In addition, BCRP actively transports highly diverse range of non-chemotherapeutic drugs and non-therapeutic compounds. High levels of BCRP expression in various tissues also suggest its importance in normal physiology. These include stem cells from a variety of tissues indicating a role in protection from xenobiotics, as well as in organs important for absorption (small intestine), distribution (blood–brain, blood–testis and maternal–fetal barriers) and elimination (liver and kidney) of drugs. Determining its molecular architecture will therefore provide an understanding of its mechanism. We aim to discover, by structural means and biochemical studies, the binding site and key residues involved in drug interaction in BCRP, which in turn will facilitate designing of highly selective inhibitors that can restore drug sensitivity in cancer cells. To this end, we have generated multiple BCRP-eGFP fusion constructs from Human as well as two other eukaryotic homologs that have shown promising overexpression in baculovirus-infected Sf9 cells.