2013 Program Project Development Grant Recipient – Simon Gayther

Simon Gayther, PhD
University of Southern California
Functional Analysis of Genetic Susceptibility Loci to Identify Biomarkers and Candidate Genes Associated with Ovarian Cancer Initiation, Progression and Outcome

Co-Investigators
Ellen Goode, PhD
Mayo Clinic

Alvaro Monetiro, PhD
H. Lee Moffitt Cancer Center

Project Summary

Genetic factors can increase a woman’s chance of getting ovarian cancer; they can also affect how well a woman responds to treatment when she has been diagnosed with ovarian cancer. Working as part of a large international team, the three principle investigators of this proposal have identified and characterized multiple genetic factors that can influence both a woman’s risk of developing ovarian cancer and the chance of survival after a diagnosis of ovarian cancer.

However, understanding how these genetic factors cause ovarian cancer and affect its treatment is largely unknown. Such an understanding requires a wide range of different expertise and an integrated research program; but the potential rewards and benefits of this research are substantial. As an example, two genes BRCA1 and BRCA2, identified in the mid-90s, significantly increase ovarian cancer risk; but understanding their function and clinical significance has led to intervention strategies to prevent ovarian cancer and novel therapeutic strategies to treat ovarian cancer. Undoubtedly their finding has saved countless lives.

We aim to use resources, methodologies and technologies we have developed over the last few years to understand the function of novel genetic markers for ovarian cancer we have already found, and to discover additional markers that affect risk and survival in ovarian cancer patients. These studies will likely lead to the discovery of genes that are responsible for the early stage development of ovarian cancer, which could lead to the development of novel biomarkers for early detection and prevention of the disease; and also the discovery of genes that could lead to the development of novel therapies for treating ovarian cancers. Overall the goal of this research is significantly reduce mortality in women resulting from ovarian cancer.

Bio

Dr. Simon Gayther is Professor in Preventive Medicine at the University of Southern California, Los Angeles. After completing his PhD in hereditary cancer genetics in 1994 (University College London, UK), Dr. Gayther moved into ovarian cancer research working with Professor Bruce Ponder at the University of Cambridge, searching for the BRCA1 and BRCA2 susceptibility genes, which are largely responsible for the breast-ovarian cancer syndrome. A major aspect of this work was understanding the role and contribution of these genes to familial ovarian cancer, and defining the variations in breast and ovarian cancer risks associated with different BRCA1 and BRCA2 mutations. Dr. Gayther continued his work in ovarian cancer susceptibility genetics after joining Professor Ian Jacobs’ team, first at Barts and the London Hospital and then at University College London. Together with Dr. Paul Pharoah at University of Cambridge, he established an international collaboration to identify common low-penetrance susceptibility alleles for ovarian cancer. This developed into the Ovarian Cancer Association Consortium (OCAC), which has since became the world’s largest population-based ovarian cancer case collection for identifying genetic and epidemiological risk factors for the disease. As part of OCAC, Drs. Gayther and Pharoah led the first genome wide association study for ovarian cancer, which has identified several novel susceptibility alleles for the disease. More recently, Dr Gayther has played a key role in developing the principles and methodologies for studying the functional significance of common low risk susceptibility alleles and the target cancer susceptibility genes at these loci, which is the focus of this OCRF award. In this new area of research, he is collaborating closely with Drs. Alvaro Monteiro (H Lee Moffitt Cancer Center, Tampa) and Ellen Goode (Mayo Clinic, Rochester), and more broadly with the NIH initiated consortium GAME-ON. The long-term aim of Dr. Gayther’s research program is to reduce mortality from ovarian cancer by: (1) developing risk prediction strategies that identify the proportion of the general population at greatest disease risk; (2) to target these women for clinical intervention strategies, such as biomarker screening for detecting early stage disease; (3) Using functional approaches, to evaluate the role of novel ovarian cancer susceptibility genes in the initiation and development of ovarian cancer, and their potential as both early stage disease biomarkers and therapeutic targets for better treatment.

This grant was made possible in part thought the generous support of the Smith Family, in memory of Kathryn Sladek Smith.