Improving Early Detection and Prevention of Ovarian Cancer
Many women are at high genetic risk of developing ovarian cancer. Strategies for early disease detection and preventive, non-surgical treatments are urgently needed. The Swedish Cancer Institute’s Paul G. Allen Research Center and the Heath Lab are collaborating to address both of these challenges.
3D still showing fallopian tube. Image credit: Scientific Animations/Wikimedia Commons, recolored by ISB.
Ovarian cancer is often highly deadly, in large part because it is typically caught only at late stages. The cancer, which kills more than 200,000 people every year around the world, manifests with few symptoms in its early stages, and no screening methods currently exist. Women who carry mutations in the genes BRCA1 and BRCA2 are 20 to 40 times more likely to develop ovarian cancer than those without these mutations; better methods for early detection and prevention are especially needed in this population. ISB’s James Heath, PhD, and Swedish Cancer Institute’s Charles Drescher, MD, are leading a project to identify the molecules that underlie ovarian cancer development in BRCA mutation carriers and to develop new ways to detect and intervene in this cancer at its earliest stages.
- Funded by Paul G. Allen Research Center at the Providence Swedish Cancer Institute
- Led by James R. Heath, PhD
- Key collaborators:
- Charles Drescher, MD, Swedish Cancer Institute
Identifying and preventing ovarian cancer before it starts
Women who carry BRCA mutations are typically counseled to have their fallopian tubes and ovaries surgically removed in a procedure called risk-reducing salpingo-oopherectomy. Because the removal of the ovaries triggers instant menopause, this surgery comes along with significant side effects and is itself invasive.
Heath and Drescher aim to study the earliest signs of the disease in this population with the goals of predicting who will develop ovarian cancer and who won’t, sparing many from unnecessary surgery, and ultimately developing less invasive ways to prevent the disease even in those with early signs of the cancer.
They are using cutting-edge pathology techniques to identify and study tiny, pre-cancerous lesions in the fallopian tubes – where most ovarian cancers originate – removed from women who have undergone this preventive surgery and comparing those tissues to those surgically removed from women with more advanced ovarian cancer.
The team is using single-cell analyses to identify genes switched on (or expressed), protein levels, and chromatin state, a measure of how receptive certain regions of DNA are to being expressed, in cells from these lesions and from healthy, non-cancerous tissue. They’re looking for gene expression or proteins whose levels are significantly different between the pre-cancerous lesions and healthy tissue from the same patients, with the goal of identifying molecules that could be used to signal early-stage ovarian cancer in a clinical test.
By better understanding the genes and proteins involved in ovarian cancer’s earliest phases, the researchers also hope to identify new targets for treatment and prevention. These studies are already yielding insights into how early-stage lesions impact neighboring, non-cancerous cells in the fallopian tube.
The researchers are also performing similar molecular analyses in blood samples from women with and without BRCA mutations to better understand how these mutations influence large-scale alterations in the carriers’ metabolism, immune system, and proteins.
Finally, they’ve established and are building up a repository of frozen tissue and blood samples representing early-stage ovarian cancer and pre-cancerous lesions. This repository will serve as an invaluable resource to support further studies of ovarian cancer detection and prevention.
Contact Dr. James R. Heath
President and Professor
ISB