The next step toward individualized ovarian cancer treatment could come in the form of honeycomb-like arrays of lab-grown cancers, according to research published in Clinical Cancer Research.
Researchers from the University of Michigan, Ann Arbor, MI, devised a process to grow hundreds of cultured cell masses, called spheroids, from just a few tumor cells derived from a patient. In a structure called a 384-hanging drop array, each spheroid is encased in a tiny droplet of a special culturing medium. This method yields cells that grow and multiply just as they would inside the body.
The hope is that these spheroids can become a testing ground for many different medications to find the best treatment combination for an individual patient. The therapies could be adjusted on the fly as the disease evolves, which can help doctors stay one step ahead of the tumor cells.
"Today, we're limited to two-dimensional cells grown in bovine serum that's derived from cows,” said Geeta Mehta, PhD, the Dow Corning Assistant Professor of Materials Science and Engineering at the University of Michigan and leader of the research team that developed the technique. “Cells grown this way often don't respond to medication the same way as ovarian cancer cells inside the body. Three-dimensional cultured spheroids provide a much more predictive way to test many different medications, and a way to grow many cultured cells from just a few of the patient-derived cells."
In their study, the researchers administered drugs to the cultured cancer spheroids and compared their response to that of ovarian cancer cells that had been removed from the same patient and implanted into mice. Results showed the response of the cultured spheroids accurately mirrored that of the natural cells implanted in the mice.
Dr. Mehta explained that even among cancers, ovarian cancer is particularly menacing. Its free-floating spheroids shuttle cancer through the abdomen with the ability to form new tumors wherever they go. The cells within those spheroids mutate often and unpredictably and can quickly develop new strains that resist chemotherapy drugs.
Patients who have had surgery to remove an ovarian tumor have a 70% relapse rate. Dr. Mehta believes these patients may one day benefit from this new technique.
The hanging drop array's hundreds of individual compartments make it possible to grow many spheroids at once and quickly gather data about multiple drugs. This is a key, as chemotherapy treatment often requires complex cocktails of multiple drugs administered together. The cells could provide a way to test many such cocktails simultaneously.
Widespread clinical use may be years in the future, but Dr. Mehta and her team are planning to conduct more extensive testing. They are aiming to culture cells from patients who are undergoing chemotherapy, then administering the same chemotherapy drugs to the cultured cells and measuring their response.
"This is a really important step to expedite personalized medicine for cancer patients," said Ronald Buckanovich, MD, PhD, a professor of medicine at the University of Pittsburgh, Pittsburgh, PA, and a senior co-author of the study. "The ability to take patients' samples, rapidly grow them in a more physiologic manner and study their response to therapy, without using mice, will be a faster, cheaper, and more humane way to rapidly test a patient's response to dozens of therapeutics."
The team also plans to expand testing of the treatment beyond cancer stem cells to other cell types with the goal of gaining a broader understanding of the role each cell type plays in building resistance to chemotherapy.
"This gets us closer to an understanding of what treatment options work best, but it also gives us a way to study exactly what happens when a treatment fails," said study co-author Karen McLean, MD, PhD, assistant professor of gynecologic oncology at Michigan Medicine. "And understanding why something doesn't work can be extremely useful as a way of developing better treatments or treatment combinations."
The research was supported by the Department of Defense Ovarian Cancer Research Program Early Career Investigator Awards and by the National Cancer Institute of the National Institutes of Health.
To read more about the study, click here.