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Alan Ashworth, PhD, FRS
President, Helen Diller Family Comprehensive Cancer Center
Senior Vice President for Cancer Services, UCSF Health
Professor of Medicine, Division of Hematology/Oncology
University of California
San Francisco, California
- Seeking to improve breast cancer outcomes by identifying new therapeutic targets for aggressive breast cancers.
- Studies are ongoing to identify novel strategies to target genetic vulnerabilities caused by mutations in the p53 gene.
- This research addresses a prevalent issue affecting multiple tumor types and has the potential to improve treatment for patients with aggressive cancers.
The p53 protein prevents tumor formation by preventing damaged cells from dividing. A normal cell will die without p53, but tumor cells thrive without its tumor suppressing activity. Dr. Ashworth is pursuing genomic studies to determine how tumor cells survive the loss of p53 to identify new approaches to kill these cells.
Full Research Summary
One of the major challenges in the treatment of breast cancer is the selection of the right treatment for the right patient. Breast cancer is a very heterogeneous disease, and research suggests that in part, the genetic makeup of the tumor determines how a patient will respond to treatment. Understanding why some women with breast cancer respond well to their treatment while others do not is critical to improve the lives of women with the disease.
The focus of Dr. Ashworth's BCRF research is to understand how various gene mutations affect tumor cell behavior and to identify targets to reduce resistance to anti-cancer therapies.
The p53 protein is a tumor suppressor that prevents damaged cells from dividing. This protein is often described as the guardian of the genome, and when p53 is lost, cells progress through the cell cycle despite the presence of DNA damage and other cellular defects, which drive tumorigenesis.
The p53 pathway is inactivated in almost all tumors, and mutations in the p53 gene have been detected in approximately 75 percent of triple negative breast cancers. Although loss of p53 is a hallmark of many cancers, inactivation can occur in many ways, and this variability has made therapeutic targeting of p53 loss difficult.
Using functional genomic approaches, this year, Dr. Ashworth and his team will look for genes that are important for the survival of cancer cells with common p53 mutations. These essential genes represent genetic vulnerabilities in p53 mutant tumors and will inform novel therapeutic strategies to treat breast cancer tumors with these mutations. In addition, because p53 mutations are prevalent across tumor types, any therapies uncovered are likely to translate to other p53 mutant cancers.
Alan Ashworth, PhD, FR, is President of the UCSF Helen Diller Family Comprehensive Cancer Center in San Francisco, a role he began in January 2015. He was previously Chief Executive of the Institute of Cancer Research (ICR) in London, United Kingdom.
In 1999 he was appointed the first Director of the Breakthrough Breast Cancer Research Centre where he was also Professor of Molecular Biology and leader of the Gene Function team. Professor Ashworth’s Directorship ended in January 2011 when was appointed Chief Executive of the ICR.
A translational biologist and laboratory researcher, Dr. Ashworth’s research focuses on understanding breast cancer genetics and applying what he learns to change the way patients are treated. He was a key part of the team that identified the BRCA2 breast cancer susceptibility gene, which is linked to an increased risk of some types of cancer. Ten years later, Dr. Ashworth found a way to kill off BRCA1- and 2-related tumor cells by treating them with PARP inhibitors, which amplifies the damage caused by the broken DNA repair machinery in those cells. This exemplifies the genetic principle of synthetic lethality in cancer therapy.
Dr. Ashworth is an elected member of EMBO and the Academy of Medical Sciences and a Fellow of the Royal Society. 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 and was the inaugural winner of the 2013 Basser Global Prize. He has also recently been selected as the recipient of the 2015 Genetics Society Medal.
BCRF Investigator Since
The Blizzard Entertainment Award