Alan Ashworth, BSc, PhD, FRS

With funding from BCRF, Dr. Ashworth aims to investigate whether a set of RNA molecules, known as micro-RNAs (miRNAs), change the way breast tumor cells respond to PARP inhibitors, a relatively new class of drug. In the first six months of the past grant year, his team developed and carried out a genetic screen that has allowed them to identify a handful of candidate miRNAs that change the way breast tumor cells respond to these drugs. In the second six months of the project, they focused on work aimed at understanding how particular miRNA molecules modify the response to drug. These experiments have led this research team to believe that the miRNAs they identified modify a process known as DNA repair.

PARP inhibitors are now showing promise in the treatment of particular types of breast and ovarian cancers. These drugs appear to be safe and can have significant effects on tumors without causing many of the side effects that are common with standard chemotherapies. Dr. Ashworth proposes to extend the use of this novel type of drug by identifying miRNAs that modify the response to PARP inhibitors, such as olaparib. To achieve this, he and his team have been carrying out high-throughput functional screens using whole genome miRNA libraries. The miRNAs discovered in these screens will then be developed as clinical biomarkers that will be used in the clinic to determine which patients are more likely to respond favorably or will be resistant to PARP inhibitors.

Mid-year Progress: Dr. Ashworth and colleagues continue their research using a library of miRNA mimetics to assess the impact of miRNAs on PARP inhibitor response. They have assessed the generality of their observations and have been able to replicate their initial findings in additional breast tumor cell lines, as well as normal breast epithelial cells. Secondly, Dr. Ashworth's team has carried out experiments that could explain the sensitization to PARP inhibitors.

Bio:
Professor Alan Ashworth FRS, is Professor of Molecular Biology, Leader of the Gene Function team in The Breakthrough Breast Cancer Research Centre and CEO of the Institute of Cancer Research (ICR).

Alan Ashworth joined the ICR in 1986 as a postdoctoral scientist in the Section of Cell and Molecular Biology and in 1999 he was appointed the first Director of the Breakthrough Breast Cancer Research Centre. The Centre is now recognized internationally as one of the leading breast cancer centers and has more than 120 scientists and researchers working on aspects of the disease, ranging from basic molecular and cellular biology through to translational research and clinical trials. Professor Ashworth's Directorship ended in January 2011 when he took up the position of Chief Executive of the ICR.

One of Professor Ashworth's major contributions has been his work on genes involved in cancer risk. He was a key part of the team that in 1995 discovered the gene BRCA2, which is linked to an increased risk of breast and ovarian cancers. Ten years later, Professor Ashworth identified a way to exploit genetic weaknesses in cancer cells including mutated BRCA2, leading to a new approach to cancer treatment.

His current research reflects his passion for the development of personalized cancer medicine, translating laboratory studies into improvements in patient care. He is also joint leader, with Professor Tony Swerdlow, of one of the world�s most comprehensive and largest (>100,000 participants), studies of breast cancer causation, the Breakthrough Generations Study (http://www.breakthroughgenerations.org.uk).

Professor Ashworth is an elected member of European Molecular Biology Organization (EMBO) and the Academy of Medical Sciences. His contributions to mammalian genetics and identification and study of inherited breast cancer susceptibility genes saw him elected as a Fellow of the Royal Society in 2008. He has been the recipient of a number of scientific prizes and awards including The European Society of Medical Oncology Lifetime Achievement Award, the David T. Workman Memorial Award of the Samuel Waxman Cancer Research Foundation and the Meyenburg Foundation's Cancer Research Award.