May 06, 2021
A research team led by Andrew Godwin, PhD, deputy director of The University of Kansas Cancer Center, and Yong Zeng, PhD, associate professor at the University of Florida, has been awarded a $3.1 million grant from the National Institutes of Health to investigate better ways to identify ovarian cancer earlier. Unlike breast, cervical or colorectal cancer, there is no reliable screening test to detect epithelial forms of ovarian cancer.
Ovarian cancers represent several distinct diseases, which are named after the type of cell they come from: epithelial, germ cell and stromal. Epithelial ovarian cancers, which represent 85 to 90 percent of malignant ovarian cancers, are a complex group of tumors that arise from multiple different precursor tissues, and the most common and deadly subtype (high-grade serous) is thought to originate primarily in the fallopian tubes. Epithelial ovarian cancer is referred to as the “silent killer” due to its lack of overt clinical symptoms. By the time a woman knows she has it, the cancer is often advanced. However, when caught early, the prognosis is excellent. Developing non-invasive and highly specific blood-based tests for pre-symptomatic screening and early detection of ovarian cancer is therefore crucial.
Dr. Godwin’s laboratory, which has received funding over the years from the OVERRUN Ovarian Cancer Foundation and the Vicki Welsh Ovarian Cancer Fund, is dedicated to finding better, more reliable methods for the detection of this deadly disease, particularly high-grade serous carcinomas, the deadliest form of ovarian cancer that primarily originates in the fallopian tubes and spreads rapidly.
“Most women with epithelial ovarian cancer will be diagnosed at a later stage when it has spread and become much more difficult to treat,” Dr. Godwin said. “There is an urgent need to identify novel biomarkers, apply new strategies and develop technologies to diagnose ovarian cancer earlier.”
Exploring the role of small extracellular vesicles
Small extracellular vesicles, often referred to as exosomes, play an important role in cancer development and progression. They are the courier of the cells - exosomes derived from cancer cells shuttle data that can be received by surrounding cells and promote signals to help the tumor grow and spread. Exosomes in blood and other bodily fluids can serve as valuable biomarkers for early warning signs of cancer, as well as indicators for how the cancer is responding to treatment.
“Most blood biomarkers to date lack the necessary sensitivity and specificity for early detection of ovarian cancer. Small extracellular vesicles, on the other hand, contain enriched subsets of biomolecules mirroring the tumor cells of origin, including certain proteins and RNAs. Even when present at lower levels, which is often the case when cancer is in its earliest phases, small extracellular vesicles serve as a promising biomarker for early detection,” Dr. Godwin said.
The grant will fund the team’s efforts to validate panels of ovarian-specific biomarkers and innovative “lab-on-a-chip” technology that can capture and detect ovarian cancer-associated exosomes. The miniaturized chips contain microscopic channels that can enrich for specific subpopulations of exosomes and measure ovarian cancer-specific protein biomarkers from just a few drops of blood.
To validate their findings, researchers will analyze longitudinal samples from two sources:
- The Early Detection Program within The University of Kansas Cancer Center’s BioBank, which contains samples from asymptomatic women undergoing their annual mammograms, and
- An international consortium following BRCA1 or BRCA2 germline mutation carriers who later developed ovarian cancer.