Discoveries Magazine


The Power of Prediction: Simon Gayther, PhD

Simon Gayther, PhD

Photo: Al Cuizon

Simon Gayther, PhD, is serious about the science of disease prediction and prevention. The renowned ovarian and breast cancer researcher — a new recruit to Cedars-Sinai and a transplant from across the pond — opens up about the challenges of assessing genetic risk factors and the joys of clowning around.

Q. Did you always know you wanted to be a cancer researcher?

A: Not at all. I’m from the English countryside and, for a while after finishing my undergraduate degree in zoology, not knowing which career to choose, I toured as a clown with a traveling circus. They were looking for someone to come and look after the animals but quickly realized that my tall and clumsy nature was perfect for dressing up to be laughed at by children.

Q. What interested you in going into breast and ovarian cancer prevention?

A: When I was working on my PhD, I fell in love with the idea that geneticists could contribute to saving lives by preventing disease. The hot topic at the time was the race to find the BRCA1 and BRCA2 genes — it was, in terms of heritable genetics, probably the most exciting story in research. Seeing how discoveries like those could translate into real impact in patients’ lives has pushed me forward and continues to do so today.

Q. How has the landscape shifted over the past 20 years in terms of combating these illnesses?

A: The answer is simultaneously exhilarating and frustrating. In 1990, five-year survival rates in women diagnosed with breast cancer were just 30 percent; today, 70 percent of women with breast cancer will be alive five years in. By contrast, for ovarian cancer, the five-year survival rates have hardly improved in five decades, mainly because it’s a very difficult disease to diagnose at its earliest stages when it is most treatable. We must change that.

Q. How are you approaching the challenge?

A: We’re looking at individuals who, based on family history, are predisposed to getting these cancers. But identifying risk is a tricky business because there are so many factors that influence it. For instance, if you are taking an oral contraceptive, or if you have given birth, your chances of getting ovarian cancer are cut in half. So conducting studies that yield meaningful results requires an extremely big patient sample size. I’m part of a consortium that comprises more than 50 different centers from around the world, pooling data from tens of thousands of people who do — and don’t — have the disease.

Q. What are the potential benefits of predicting genetic risk if there are no cures?

A: It’s the promise of precision medicine: tailoring our approach to healthcare depending on a person’s background and needs. What genetics is doing is allowing us to imagine a future in which, based on individual screening, we can give a woman actionable advice. Perhaps, based on the thousands of genetic variations that contribute to her specific risk for something like ovarian cancer, we can suggest that she have children early and then elect for a surgical intervention to remove the at-risk organ. For someone who is at lower risk, we can recommend entering her into a screening program so that when she turns, say, 40, we start to monitor her for any signs or symptoms of the disease.

Q. Can genetic profiles offer clues about why some women won’t develop hormonal cancers?

A: When we talk about genetics, we often think of the risk factors that make us susceptible to disease. But we’ve all heard of people who smoked their whole lives and never got lung cancer. The same way our genes can help dictate what happens to us, they can also offer us a measure of protection from certain illnesses. Part of our work is unlocking the mystery of these safeguards. This has major real-world implications for hormonal cancers because we currently spend huge amounts of time and money on screening the entire population using mammography. If we could pinpoint who isn’t likely to get a disease, we could be investing our resources in screening only the people who are most at risk.

Q. Ever miss the clown business?

A: It was an oddly fitting start to my real career since it taught me that, every time you fall down, you just get right back up again.

Simon Gayther, PhD

Director, Molecular Epidemiology, and co-director, Center for Bioinformatics and Functional Genomics, Cedars-Sinai Department of Biomedical Sciences

Fruitful Collaboration
Together with Paul Pharoah, PhD, at the University of Cambridge, and Beth Karlan, MD, at Cedars-Sinai, Gayther has established many international collaborations to identify the genetic causes of ovarian cancer. This developed into the Ovarian Cancer Association Consortium, now the world’s largest population-based ovarian cancer case collection, comprising almost 50,000 subjects. Karlan is director of the Women’s Cancer Program in the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute, and the Board of Governors Chair in Gynecologic Oncology.

Even More Fruitful Collaboration
Wife Kate Lawrenson, PhD, is also an ovarian cancer investigator at Cedars-Sinai. The couple had their first child this summer.

Former Life
Used to be the lead singer in the rock band The Shifting Balance — a name based on an evolutionary theory hypothesizing that the interaction among natural selection, genetic drift, and migration is more important than the action of any single force.

This interview has been edited and condensed.

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