Q&A with Alan Ashworth, President, UCSF Helen Diller Family Comprehensive Cancer Center, Recipient of the PMWC 2018 Pioneer Award

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[et_pb_accordion_item title=”Q: How did you become interested in breast cancer and the role of BRCA2?”]

A: I was PI of a lab studying the structure and regulation of genes at a basic level. Then at the end of 1994, a colleague Mike Stratton, asked if I could help him with a project. This turned out to be the identification of the BRCA2 cancer susceptibility gene. Subsequently I became very interested in why people with defective BRCA1 or BRCA2 genes develop cancer and what we might do to treat and prevent such cancers.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: What led you to the discovery of PARP inhibitors for the treatment of cancer?”]

A: We and many others worked out that BRCA-deficiency causes a defect in DNA repair and this is what, at least in part, causes an increase in cancer risk. But this did not immediately give us much insight into how we might treat cancers arising in BRC-mutation carriers. Most cancer treatments attack the enhanced ability of cancer cells to grow and survive and here we were dealing with a deficit. So, it took us a while to think about vulnerabilities in BRCA mutant cells and how we might exploit them. Our first pass at this was thinking about the use of the platinum chemo- drugs and does turn out that these are quite good for treating BRCA mutant tumors. However, the real insights came when we started to investigate other DNA repair pathways. Working with a company called Kudos we tested whether drugs called PARP Inhibitors might be efficient at killing BRCA-mutant cells through a mechanism called synthetic lethality. We saw astonishing sensitivity compared to normal cells and these results were enough to propel PARP inhibitors into the clinic for the treatment of BRCA-related cancers.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: What is the mission of the Center for BRCA Research at UCSF?”]

A: We’ve known for two decades how to identify BRCA mutation carriers, and the past few years have brought about new treatments for BRCA-mutated cancers. Building on this, UCSF’s Center for BRCA Research, one of only two such centers in the US, personalizes the care we provide to patients and families with BRCA and other inherited mutations, and it allows what we learn from them to drive our research priorities. These are to build on the use of PARP inhibitors to develop better treatments and also to do research to work out how to prevent cancer in mutation carriers. One of the new aspects of this is that care and research are driven by the underlying genetic defect rather than where the cancer occurs which is the traditional approach.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: What would be the benefits that the new UC Cancer Consortium bring to patient care?”]

A: The UC Cancer Consortium is a partnership between the five UC academic cancer centers, which collectively are home to some of the best scientists and physician researchers to be found anywhere. That we all are conducting cancer research and providing care in the most ethnically-diverse state in the US puts us in a position to do unique things in precision care and precision public health. Specifically, we can expand clinical trials, tailor trials for ethnically-diverse populations, develop prevention programs for different populations, share big data to better inform protocols, and advocate as a group to improve public healthcare policy.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: Can you share some of the latest discoveries in new drugs and diagnostics that scientists at the Helen Diller Family Comprehensive Cancer Center are working on?”]

A: We have a tremendous amount of activity in this area. One example is Trevor Bivona leading a new program on drug resistance – a key limitation of targeted therapy. I am also very excited by Kevan Shokat’s work on targeting Ras. We have a lot of work on immunotherapy including the development of markers of who will respond. Finally Wendell Lim and colleagues are leading the way on the next generation of cellular therapies.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: Can you tell us about SF CAN?”]

A: SF CAN is a new long-term community-based initiative designed to reduce cancer-related morbidity and mortality in San Francisco that I co-founded with Bob Hiatt of UCSF. It is a partnership of individuals and institutions concerned with cancer control in the city, including the City and County government, the Department of Public Health, community groups and cancer care institutions, while UCSF provides administrative leadership and an organizational structure. Our goal is to reduce both the cancer burden and disparities in cancer occurrence and outcomes in the City of San Francisco by harnessing innovative science, new technologies, and our knowledge of community needs. As far as we know this is the first time a City in the US has taken such a comprehensive approach to tackling cancer so we excited to be trying something innovative.

[/et_pb_accordion_item][et_pb_accordion_item title=”Q: What advice can you give to young scientists considering academic research career?”]

A: I think you need a very clear idea of what big problem you are trying to solve in a 5 or 10 year time frame. I ask people I interview this a lot and frequently the answer I get is a list of experiments rather than a vision. I would also encourage people to be bold and to try to make a big impact and change the world. Academic research is an increasingly difficult career path so if you are going to do it you might as well go full tilt.


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