Despite significant gains made in cancer diagnosis and treatment over the last 50 years, ovarian cancer remains the second most common, as well as the deadliest, of all gynecological cancers in the United States. Ranking fifth in cancer deaths among women, it accounts for more deaths than any other cancer of the female reproductive system.

Women face a 1 in 78 risk of receiving an ovarian cancer diagnosis. The odds of dying from ovarian cancer are about 1 in 108. In 2022 alone, the American Cancer Society estimates that close to 20,000 women will be diagnosed with ovarian cancer.

Of those 20,000 women diagnosed, it is predicted that nearly 13,000 will die from the disease. The high mortality rate is largely due to inadequate early screening diagnostics and a high rate of recurrence.

Presently, the survival rates are not very promising. Of those diagnosed, 70% will survive for 1 year or more; 45% will survive their cancer for 5 years or more, and 35% will survive for 10 years or more.

Dr. Sarah Cooper of HudsonAlpha

To gain a better understanding in hopes of developing a more effective treatment protocols, clinical researchers at HudsonAlpha in collaboration with The University of Alabama at Birmingham (UAB) recently published a paper in Clinical Cancer Research. The paper elaborates on a study that explores gene expression and metabolic signatures in ovarian cancer, in hopes of discovering both markers of treatment response and potential therapeutic targets.

HudsonAlpha Faculty Investigator Sara Cooper, PhD, and longtime clinical collaborator Rebecca Arend, MD, an assistant professor in the UAB Division of Gynecologic Oncology, along with associate scientists in the Experimental Therapeutics Program at the UAB Comprehensive Cancer Center, have been working together to identify new drugs, drug targets, and combinations of drugs to overcome present ovarian cancer treatment limitations.

Along with the three types of ovarian cells – epithelial cells, germ cells, and stromal cells, cells that have the potential for tumor development, there are also tumor subtypes of ovarian cancer, each with its unique clinical features. These subtypes often present a challenge to quickly finding a non-invasive way of determining the best therapy protocol, to observe whether a treatment is effective, or even predict whether a cancer might reoccur.

In the study, the research team set out to integrate gene expression data and metabolic data from tumors and benign tissue to gain a more complete picture of a type of epithelial ovarian tumor called high-grade serous ovarian carcinoma.

“Our study combined gene expression profiles with metabolic analysis in tumors to try to identify new pathways that can be targeted for treatment,” says Cooper. “We found diverse gene expression and metabolic differences across subtypes of high-grade serous tumors, which supports the use of genomic and metabolic information to help select treatments and predict treatment outcomes on an individualized basis.”

Most of the current genomics research probes primary tumor tissue. However, important clues for how to treat patients, especially those with recurrent disease, can be found in patient samples taken after treatment or from outside the primary tumor.

The research team compared pre-treatment and post-treatment tumor tissue to study individual responses to chemotherapy. They found that chemotherapy caused changes in gene expression and activity of the WNT signaling pathway.

“One of the things we’ve been interested in is the role of the WNT signaling pathway,” said Cooper. “WNT is essentially a set of genes that are important for the development of cancer. The set of genes are able to signal the cell to proliferate and do other things that are important for cancer cells, that we’ve known about for quite some time. Our work recently has shown that when this pathway is activated, it also impacts how well immunity cells can recognize and infiltrate a tumor and that has important implications for whether our body’s own immune system can recognize tumor cells and help the body get rid of those tumor cells that we don’t want to be there.”

The altered WNT activity in post-chemotherapy tumor tissue was found to be connected to a weakened immune response in the tumor, suggesting that WNT signaling could be a promising therapeutic target to enhance immune function.

Ascites is a fluid buildup that is experienced by many women with ovarian cancer and is known to contribute to poor patient outcomes by accelerating metastasis and increasing the likelihood of therapeutic resistance.

Findings indicate that ascites contains a subset of resistant, more stem cell-like cells, which likely contribute to disease recurrence. Analysis of post-treatment tissue and ascites fluid could help better inform treatment decisions and monitor disease recurrence.

“In that fluid, there are cells that are either derived from the tumor itself, of have come off the tumor, as well as other immune cells,” said Cooper. “We were interested in understanding whether the cells that are in the ascites, which represent more of a metastatic-type cell would be the same or different than the ones that are found in the primary tumor. What we saw was that were some pretty significant differences between those two cell types even though they came from the same patient.”

Additionally, the study evaluates the challenges in determining precision medicine approaches for ovarian cancer patients. It also supports the use of genomic and metabolic information to help select treatment, predict treatment outcomes, and identify potential new therapeutic targets to achieve better outcomes for ovarian cancer patients.

Cooper also leads Information is Power, a genetic testing initiative. The testing evaluates several dozen genes that are associated with increased risk for breast, ovarian, colon, and endometrial cancers. Over the past six years, the program has offered free or reduced-cost genetic tests to residents living in five North Alabama counties.

To reach medically underserved areas throughout Alabama, Information is Power has recently expanded beyond North Alabama through its collaborations with #NowIncluded and Montgomery area physicians.

“I really enjoy the work that I get to do, not only because I work with a great team of people and through the Information is Power program, but we also have a great opportunity to work with the community,” said Cooper. “I feel privileged that I have the opportunity to do even something small that has the potential to change things for the better – for people that are facing a cancer diagnosis”

To learn more, visit hudsonalpha.org.