Identification and functional validation of additional therapeutic targets in HER2 amplified breast cancers
Research team: Molecular Pathology Team
Project Summary
Breast cancer is a heterogeneous disease which encompasses entities that have distinct biological characteristics and clinical behaviour. HER2-positive tumours account for approximately 25% of all breast cancers. Treatment of such patients has dramatically improved with the addition of therapies targeting the HER2 receptor including Herceptin. However, a substantial number of patients have de novo resistance (i.e. the drug does not have any effect) or will acquire resistance after receiving such treatment. Microarray-based profiling analysis has shown that there are several genetic changes which correlate with aberrant gene expression in HER2 positive breast cancers. The proteins expressed by these highly amplified genes may well be essential for the survival of the cancer and may not only modulate resistance to anti-HER2 therapy, but also additional therapeutic targets for these cancers.This project will study a large series of HER2 positive cancers and cell lines (i.e. tumour cells that we can grow indefinitely in laboratory dishes) with techniques that will provide a detailed survey of the copy numbers and activity of every gene in HER2 positive disease. Identifying these genes that are upregulated and essential for the survival of HER2 positive cells may allow us to understand the mechanisms behind resistance to anti-HER2 therapy and aid the development of potential new therapeutic targets. This may also enable us to identify predictive and prognostic markers of response to anti-HER2 therapy and better understand the biological diversity of this disease. We hope that the results of the project will increase the evidence-based development of rational, tailored therapy for patients with HER2 positive breast cancer.
Biography
Dr. Shiu is a 3rd year Medical Oncology SpR on the North London Rotation. Prior to starting his PhD he most recently spent one year at University College Hospital, treating patients with colorectal, upper gastrointestinal and ovarian cancers. Throughout his training he has also involved in the recruitment and management of patients in several Phase II and III trials.He entered Guys’ & St Thomas’ Medical & Dental School in 1993, completing an Intercalated BSc (Hons) in Experimental Pathology in 1996. He graduated with his MBBS in 1999, followed by the MRCP in 2004.
Outside of the workplace, Kai-Keen is a skilled pianist and violinist and has performed with both the University of London and Guy’s and St Thomas’ Orchestras.
