Sir Bruce A. J. Ponder, PhD, FRCP, FRS

2012-2013 BCRF Project:
(made possible by generous support from The Housewares Charity Foundation)
Co-Investigator: Christina Curtis, PhD, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA

Drs. Ponder and Curtis have made substantial progress in developing approaches to study the heterogeneity of individual breast cancers. Their current efforts are focused on characterizing the extent of this intra-tumoral diversity and identifying the molecular drivers that characterize both large and small families (clonal populations) of cancer cells as these may represent actionable mutations. With the technological and computational tools in place, Drs. Ponder and Curtis aim to extend their novel approach to larger numbers of representative samples from the patient population so that their findings may be generalized to improve patient care and in the development of individualized therapies.

This approach represents a paradigm shift in the molecular profiling of breast cancer that will address unanswered questions concerning the variability in tumor phenotypes and treatment response. This research will also shed light on underlying mechanisms of tumorigenesis and may help to clarify the contributions of cancer stem cells and clonal evolution to tumor heterogeneity. With the experimental and computational tools in hand, this team will continue their efforts to reconstruct the subclonal ancestry of cell populations within an individual tumor and their associated mutational events. In particular, they will focus on identifying the molecular drivers that characterize both rare and dominant clonal populations, as they may represent actionable mutations.

Drs. Ponder and Curtis have now applied their novel experimental and analytical framework in order to interrogate the mutational diversity and subclonal architecture of a subset of breast cancers. Their approach is unique in that it enables the quantification of intra-tumor heterogeneity and tumor dynamics, with implications for personalized treatment. This team will observe extensive intra-tumoral heterogeneity on multiple spatial scales, as well as variability in tumor organization between patients, and are now analyzing additional samples in order to determine the clinical relevance of their findings.

Mid-year Progress: Drs. Curtis and Ponder will continue to investigate the evolutionary dynamics underlying tumor progression and therapeutic resistance. In particular, using high-throughput genomic data derived from breast cancer samples, they will measure patient-specific parameters such as the fraction of cancer stem cells, mutation rate, and the extent of genetic heterogeneity, and will determine whether these features are associated with clinical outcome. Using these and other data, they will exploit their computational framework in order to predict optimal treatment strategies.

Bio:
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.