Two Baylor College of Medicine researchers have received three-year grants totaling $1.35 million from the Ovarian Cancer Research Fund for studies directed toward earlier detection of ovarian cancer.

Ovarian cancer is the ninth most common cause of cancer among U.S. women and the fifth most common cause of cancer deaths in women. An estimated 22,000 will be diagnosed with the disorder this year and more than 15,000 will die of it.

Screening tests

Dr. Martin Matzuk, professor of pathology and immunology at BCM, received $900,000 for a three-year program project development grant from the Ovarian Cancer Research Fund for research into the early molecular events in the development of ovarian cancer, work that could lead to sensitive and specific screening tests. Dr. Shannon Hawkins, assistant professor of obstetrics and gynecology at BCM, has received a $450,000 Liz Tilberis Scholar Award from the Ovarian Cancer Research Fund to study the link between endometriosis and clear cell ovarian cancer.

"The goal of our team is to develop integrated screening assays that make use of the most current biomarker technology to detect and distinguish ovarian cancers at the earliest stages of development," said Matzuk. Both are also members of the NCI-designated Dan L Duncan Cancer Center (DLDCC) at BCM.

His program project grant consists of three projects:

-Discovery of early protein biomarkers of serous ovarian cancer. He will use a special mouse model that develops ovarian cancer in much the same way seen in human women. He will lead the project and Hawkins is co-leader.

-Defining all the proteins, including variants, that are secreted from ovarian cancers that can function as biomarkers found in the blood. Dr. Laising Yen, assistant professor of pathology at BCM, will lead the project and Dr. Matthew Anderson, assistant professor of obstetrics and gynecology at BCM, will co-lead.

-Identifying the metabolic changes that occur in the blood when women develop ovarian cancer. The project involves the use of state-of-the-art equipment and technology and will also seek to determine if it is possible to distinguish between aggressive forms of the disease. Dr. John McDonald will lead the project and Dr. Facundo Fernández and Dr. Alexander Gray, all of the Georgia Institute of Technology, will co-lead.

Dr. Donna Coffey of the Methodist Hospital will head the serum (blood) core and Dr. Chad Creighton, associate professor in the Duncan Cancer Center of BCM, will lead the biostatistics and bioinformatics cord.

Investigating ARID1A

Over the next three years, Hawkins will research why some women with endometriosis (the growth of cells that usually line the uterus outside that organ, often on the ovary) go on to develop a kind of ovarian cancer known as endometrioid or clear cell ovarian cancer.

"Additionally, women with endometriosis-associated ovarian cancer have a better prognosis than women without endometriosis," she said.

She will look at a gene called ARID1A that may play a role in the transformation from endometriosis cells to ovarian cancer cells. How ARID1A plays a role in the formation of tumors is not yet understood, and Hawkins plans to study both benign and malignant human tissue to find mutations in ARID1A. She will work in cell cultures to determine if ARID1A leads to increased growth of cancer cells because of interaction with other cancer genes. She will create a mouse model to mimic the low levels of ARID1A and see how early tumors form as well as to study potential therapies.

Individualized methods of treatment

"I hope this research will result in new, individualized methods of treating ovarian cancer and allow doctors to test patients with endometriosis before it progresses further," said Hawkins.

Matzuk and Hawkins pointed out that much of the early work in this field by members of the team was supported by the Young Texans against Cancer, the Partnership for Baylor College of Medicine, and the NCI-designated Dan L Duncan Cancer Center at BCM. Hawkins also credited a Career Development Award from The University of Texas MD Anderson Cancer Center with helping to boost her early work.

"This seed funding is critical to advancing science and making it possible for investigators to take on projects that might otherwise go undone," said Matzuk.

Ovarian Cancer Research Fund is the largest private philanthropy in the United States dedicated exclusively to funding ovarian cancer research.