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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 mutations in the p53 gene, which acts as a tumor suppressor to prevent damaged cells from dividing. Identifying vulnerabilities in cancer cells with specific mutations in p53 could inform novel therapeutic strategies for breast cancer patients.
What’s next: The team will look for genes that are important for the survival of cancer cells with common p53 mutations.
Research suggests that in part, the genetic makeup of the tumor determines how a patient will respond to treatment. Dr. Ashworth is studying how various gene mutations affect tumor cell behavior and to identify targets to reduce resistance to anti-cancer therapies. He and his team are focused on the p53 gene, which plays a central role in limiting cancer development and progression and is the most commonly mutated gene across all cancers. They hope to discover pathways that can be targeted to inhibit the growth of p53 mutated cells in patients with breast cancer.
Full Research Summary
Research area: Understanding how various gene mutations 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 fact that the genetic makeup of the tumor determines how a patient will respond to treatment. 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 studying a gene called p53 that acts as a tumor suppressor to prevent damaged cells from dividing. The p53 pathway is inactivated in more than half of all tumors, and p53 mutations have been detected in approximately 75 percent of triple negative breast cancers.
What he’s accomplished so far: Dr. Ashworth is using functional genomics to define vulnerabilities in cancer cells with specific alterations in p53, with the goal of identifying pathways that can be targeted to inhibit the growth of these cells.
What’s next: Dr. Ashworth 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 that can be used develop to novel therapeutic strategies to treat breast cancer tumors with these 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