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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
Goal: To improve breast cancer outcomes by identifying new therapeutic targets for aggressive forms of the disease.
Impact: Dr. Ashworth is studying genes that are critical to breast cancer proliferation and survival. These studies could unveil new vulnerabilities in cancer cells and inform novel therapeutic strategies for breast cancer patients.
What’s next: The team will study genes that are important for the survival of cancer cells and promote drug resistance.
Research suggests that the genetic makeup of the tumor influences how a patient will respond to treatment. Dr. Ashworth is studying how various gene mutations affect tumor cell behavior to identify targets to reduce resistance to anti-cancer therapies. He and his team are focused on genes that cause BRCA-mutated breast cancer cells to become resistant to PARP inhibitors, which block a critical DNA repair pathway. In addition, he and his team are investigating genetic dependencies associated with mutations in the p53 gene, which plays a central role in limiting cancer development and progression. They hope to discover pathways that can be targeted to inhibit breast cancer growth.
Full Research Summary
Research area: Understanding how various genes affect tumor cell behavior and to identify targets to reduce resistance to anti-cancer therapies.
Impact: While many advances have been made in the treatment of breast cancer, not all patients respond to available therapies. This is partly due to the genetic makeup of the tumor. Dr. Ashworth aims to identify genetic vulnerabilities in breast cancer that can inform novel therapeutic strategies for patients.
Current investigation: He and his team are investigating how specific genes promote resistance to PARP inhibitors in BRCA-mutated breast cancer. In addition, they are studying genes that are essential for cancer cell survival when p53, a tumor suppressor, is mutated. This occurs in approximately 75 percent of triple negative breast cancers and the goal is to identify new vulnerabilities in the cell that could be targeted in these cancers.
What he’s accomplished so far: Dr. Ashworth recently completed a screen for genes that cause BRCA-mutated breast cancer cells to become resistant to the PARP inhibitor olaparib and identified several interesting candidates. He and his team have built CRISPR libraries targeting proteins that are important for the survival of cancer cells with common p53 mutations.
What’s next: In the coming year, Dr. Ashworth will work to establish how the expression of the target genes they have identified promotes resistance to olaparib. He and his team will also analyze DNA and RNA samples collected from patients treated with olaparib and an immune checkpoint inhibitor to look for biomarkers that correspond with response. Dr. Ashworth has also begun initial studies to look for dependencies associated with specific p53 mutations.
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 Women's Cancer Research Fund Award