Research Topic
Molecular oncology, pathology and genetics of breast cancer

Research Description
My research interests focuses on investigating the underlying molecular mechanisms contributing towards drug resistance in the treatment of breast cancer. This includes cancer genetics, biomarker identification and the development of novel targeted therapies. It is a multidisciplinary endeavor aimed at integrating basic science research with clinical and translational studies for the development of new therapeutics and involves the contribution of basic scientists and clinicians from various disciplines.

Our team identified BQ323636.1, a novel splice variant to the NCOR2 gene associated with tamoxifen resistance and raised a monoclonal antibody targeting the epitope unique to this variant, which has been shown to be a robust biomarker to predict tamoxifen resistance and for which a Patent Cooperation Treaty has been filed. In this way more appropriate alternative therapy can be given at an early stage which can save patients from the side effects/risks of inappropriate treatment by tamoxifen. BQ can bind to NCOR2, forming a defective co-repressor complex for suppression of transcription factor signaling. More recently, we found BQ overexpression enhanced antioxidant genes expression by upregulating NRF2 transcriptional activity on the antioxidant-response element, leading to cytotoxic drug resistance in breast cancer. We are also investigating its role in conferring Aromatase Inhibitor resistance in post-menopausal women with estrogen receptor positive breast cancer.

We also developed a multidisciplinary platform making use of Ivabradine, an FDA approved HCN (Hyperpolarization-activated cyclic nucleotide-gated channel) blocker used clinically to treat chronic angina, to effectively suppress breast cancer growth without the side-effects produced by conventional chemotherapeutic agents. Provisional patent has been filed for the novel use of Ivabradine particularly as treatment for triple negative breast cancer, as well as other types of cancer. Our long term goal is to translate these areas of research into clinical trials, thus bridging the gap between laboratory and the clinics for the benefit of patients in Hong Kong and worldwide.