Honeycomb-like arrays of tiny, lab-grown cancers could one day help doctors zero in on individualized treatments for ovarian cancer, an unpredictable disease that kills more than 14,000 women each year in the United States alone.
A new process can grow hundreds of cultured cell masses, called spheroids, from just a few tumor cells derived from a patient. Grown in a structure called a 384-hanging drop array, each spheroid is encased in a tiny droplet of a special culturing medium. The 3D method yields cells that grow and multiply just as they would inside the body.
Eventually, those spheroids could serve as a testing ground where doctors could quickly try out a variety of different medications to find the best combination for an individual patient and adjust on the fly as the disease evolves, helping to stay one step ahead of tumor cells.
Ovarian cancer’s free-floating spheroids shuttle cancer through the abdomen with the ability to form new tumors wherever they go.
“Today we’re limited to two-dimensional cells grown in bovine serum that’s derived from cows. Cells grown this way often don’t respond to medication the same way as ovarian cancer cells inside the body,” says Geeta Mehta, assistant professor of materials science and engineering at the University of Michigan.
“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.”
Researchers administered cancer 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. The response of the cultured spheroids accurately mirrored that of the natural implanted cells. The findings appear in Clinical Cancer Research.
Even among cancers, ovarian cancer is particularly menacing, Mehta says. Its free-floating spheroids shuttle cancer through the abdomen with the ability to form new tumors wherever they go—the liver, the intestines, the abdominal wall. And the cells within those spheroids mutate often and unpredictably, quickly developing new strains that resist chemotherapy drugs.
Ovarian cancer’s deadly adaptability contributes to a 70-percent relapse rate among patients who have had surgery to remove a tumor. It’s these patients who Mehta believes may one day benefit from the 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 key, as chemotherapy treatment often requires complex cocktails of multiple drugs administered together. The cells could provide a way to test many cocktails simultaneously.
“…understanding why something doesn’t work can be extremely useful as a way of developing better treatments or treatment combinations.”
While widespread clinical use is likely years off, Mehta says the team now plans to do more extensive testing, culturing 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,” says senior coauthor Ronald Buckanovich, professor of medicine at the University of Pittsburgh.
“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,” says coauthor Karen McLean, assistant professor of gynecologic oncology at the University of Michigan.
“And understanding why something doesn’t work can be extremely useful as a way of developing better treatments or treatment combinations.”
The Department of Defense Ovarian Cancer Research Program Early Career Investigator Awards and the National Cancer Institute of the National Institutes of Health supported the work.
Source: University of Michigan