Alan Ashworth, BSc, PhD, FRS
Professor, Molecular Biology and Director, The Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, London, UK
2009-2010 BCRF Project:
(made possible with generous support from Hard Rock Café, Inc.)
PARP inhibitors, a relatively new class of drugs, are now showing promise in the treatment of particular types of breast cancer. These drugs appear to be safe and can have significant effects of tumors without causing many of the side effects that are common with standard chemotherapies.
Many cancer drugs are used as combinations, where they are combined with other drugs. Using drugs in this way can not only maximize the effect they have on tumors but can sometimes mean that each individual drug can be used at a lower dose, something that is often beneficial to the patient. For these reasons, Dr. Ashworth and colleagues plan to identify which drugs PARP inhibitors should be combined with. To do this they will screen a large library of drugs, the majority of which are already used in the clinic, to identify those that work better with PARP inhibitors than either drug alone. They hope to use the information to then set up clinical trials. Ultimately, the researchers hope that this work will mean that PARP inhibitors could be used more effectively in the clinic and also in a wider number of patients.
Mid-Year Progress Report:
Since October, Dr. Ashworth and colleagues have been putting together the library of drugs to screen. In total they aim to screen 2500 drugs that are already used in the clinic. They have now put this collection together and have also been optimising the screening procedure. The screens will be carried out on a large robot and the researchers now put in a significant amount of time dedicated to programming the robot prior to the initiation of the screen proper. As part of this "optimization" procedure they have been assessing whether they can detect some of the known ways in which PARP inhibitors complement existing drugs. To do this they have been carrying out test screens using a drug known as temozolomide as well as an additional agent, known as an ATM inhibitor. Using these drugs has enabled the researchers to optimize their screening procedure. They are now carrying out larger pilot screens to refine the entire procedure.
Bio:
Alan Ashworth FRS, is Professor of Molecular Biology and Director of The Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London. He was the first Director of the Centre which now contains around 120 scientists and researchers working on aspects of breast cancer ranging from basic molecular and cellular biology through to translational research and clinical trials.
Ashworth contributed to the discovery of the BRCA2 gene in 1995 and ten years later, his team identified the synthetic lethality between BRCA mutations and PARP inhibitors. The exquisite sensitivity of BRCA1 or BRCA2 mutant cells to PARP inhibitors forms the rationale behind clinical trials that are now assessing the potential of these agents.
Ashworth's other research interests are wide ranging and include high-throughput genomic and functional approaches to the study of cancer. Ashworth is an elected member of EMBO and the Academy of Medical Sciences. In 2008, he was elected as a Fellow of the Royal Society for his major contributions to mammalian genetics and the developments of new therapeutic approaches for cancer. He was recently awarded the European Society of Medical Oncology (ESMO) lifetime achievement award.
