Sir Bruce A. J. Ponder, PhD, FRCP, FRS
La Ka Shing Professor of Oncology
Co-Director, Hutchison/MRC Research Center
University of Cambridge
2013-2014 BCRF Project:
(The Housewares Charity Foundation Award)
Co-Investigator: Christina Curtis, PhD, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA
Dr. Ponder's research aims to find out who is at greatest risk of breast cancer, and why, so that we can improve early diagnosis and prevention.
Just as the shape of a face can run in families, so can risks of cancer. This sort of family resemblance is the result of the different combinations of hundreds of subtle genetic differences between each individual. It is like a genetic "hand of cards" dealt out at conception: some will get a good hand in terms of breast cancer, some a bad hand, and most will be somewhere between.
These effects can be quite large. Dr. Ponder's group has shown that about half of all breast cancers probably occur in the 12% of women who have the highest risk. If the researchers knew who these women were, they could offer them more intensive screening; and if they knew why these women were at risk, scientists might be able to find new approaches to prevention.
In the last few years, progress has been made in finding the genes that make up this "hand of cards." Dr. Ponder's laboratory published the first comprehensive study. But they still do not know what all the genes are, nor what they do. There are hundreds of these genes, and they have their effects in combination. If Dr. Ponder's team can get a handle on that combined effect, it should be much easier to understand the mechanism than if they try to study each gene separately – as researchers do now. And the combination should tell them in one go about all the genes, including the ones we have not found.
The normal tissues of the body are controlled by networks of genes, responding to the environment and precisely controlled by feedback loops. They think that the subtle effects of the "bad hand" of breast cancer genes work together to upset the balance of these gene networks.
Dr. Ponder's team aims to find out in detail what these networks are, how they are changed by the breast cancer genes, and in how many different ways. They hope this will tell us how many different mechanisms there are, which mechanism is faulty in which women and – eventually – how for each mechanism they might set out restoring the network balance to make it less likely that a cancer will develop.
Professor Ponder is working on two BCRF-supported projects.
(1) New ways to identify the important changes within each of the genes that are associated with breast cancer risk: His team’s recent work has suggested a quicker and easier way of pinpointing which of the tens or hundreds of slight genetic differences in each gene between different people, are those that are most likely to be affecting cancer risk. If they can extend this method to analyze many genes at once, it should speed up breast cancer genetics research by allowing researchers to focus on the genetic changes that really matter, and not on those that don't.
(2) How do the genes cause increased risk? It is the combination of small effects in many hundreds of genes that makes up a woman's risk of breast cancer. Dr. Ponder’s group is using "network" approaches, in which they examine how the combination of genes together disturbs the regulatory balance within a cell. Excitingly, their results suggest that although there are hundreds of risk genes, in combination they may only work through a relatively small number of mechanisms. These are early results, but if they hold up, they may suggest new ways of prevention by targeting the mechanisms that are discovered.
Bruce Ponder obtained his BA degree with First Class Honours in 1965 at the University of Cambridge, and qualified in medicine (MB, BChir) in 1968 from Cambridge and St Thomas' Hospital, London. He trained in internal medicine in various NHS posts in London, and subsequently in medical oncology at St Bartholomew's Hospital, London and at the Dana Farber Institute in Boston. He became a Member of the Royal College of Physicians in 1970, and was elected Fellow in 1987. He obtained his PhD from University College London in 1977.
From 1980, he held a Cancer Research Campaign Career Development Award at the Royal Marsden Hospital and Institute of Cancer Research in London, subsequently becoming Head of the newly founded section of Human Cancer Genetics and Reader in Cancer Genetics. In 1989 he moved to Cambridge, where in 1993 he was appointed Professor of Human Cancer Genetics, and in 1996 Professor and Head of the University Department of Oncology. He co-founded the Strangeways Laboratories for Genetic Epidemiology with Professor Nick Day in 1997; in 2005 he was appointed the founding Director of the new Cancer Research UK Cambridge Research Institute.
His research has focussed on inherited susceptibility to human cancer. He set up one of the first familial cancer clinics in the UK, and his laboratory work has contributed to the identification of susceptibility genes for thyroid, breast and ovarian cancer.
Bruce Ponder was the first Chairman of the International Breast Cancer Linkage Consortium; he initiated the UK Familial Ovarian Cancer Register and the UK Multiple Endocrine Neoplasia Type 2 Study. He was the founding editor of the journal "Breast Cancer Research". He has served on the Scientific Committee of the Cancer Research Campaign and Cancer Research UK, and as a member and Chairman of the Scientific Advisory Board of the International Agency for Research on Cancer, Lyon. He is a member of the Board of Directors of the American Association for Cancer Research (2008 - 2010).
Awards include the Public Service Award of the United States National Neurofibromatosis Association in 1992; the Hamilton Fairley Award of the European Society of Medical Oncology (2004); the Bertner Award of the MD Anderson Tumour Hospital (2007); the Alfred Knudson Lecture of the US National Cancer Institute (2008). He was a founder member of the UK Academy of Medical Sciences (1998); elected a Fellow of the Royal Society of London (2001); and awarded a Knighthhood "for services to medicine and health care" in 2008.
Dr. Ponder will serve as President of the British Association for Cancer Research from October 2010 until Sept 2014.