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Alan Ashworth, PhD, FRS
UCSF 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 targets to prevent drug resistance.
Studies are ongoing to improve response to PARP inhibitor therapy in cancers caused by mutations in the BRCA genes.
This research will lead to better outcomes for patients with BRCA-mutant tumors and identify new groups of patients that can benefit from PARPi.
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 the genetic makeup of the tumor in part, 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 if we are to improve the lives of those 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.
Individuals with BRCA1 or BRCA2 mutations are at high risk of breast and other cancers. Tumors arising in these individuals are often sensitive to PARP inhibitors (PARPi). This class of drugs has shown remarkable success in the treatment of BRCA1- and BRCA2-mutant tumors, including a significant benefit in patients with advanced breast cancer.
Despite these successes, tumors frequently become resistant to therapy. Using novel functional genomic approaches, Dr. Ashworth and his team will investigate mechanisms of resistance and identify novel genetic vulnerabilities that can be exploited by PARPi treatment.
Findings from these studies will lead to improved outcomes for patients with BRCA-mutant tumors and identify new groups of patients that can benefit from PARPi.
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.