It takes only a few hours for ovarian cancer cells to come off of the original mass and spread throughout the abdomen, quickly forming tiny clumps of tumor cells called spheroids. When serous ovarian cancer progresses to this point, the patient has less than a 30 percent chance of survival.

This type of ovarian cancer is fast-growing, quick to spread, and difficult to detect early. However, researchers in Eva Schmelz’s laboratory at Virginia Tech recently found that the ovarian cancer cell spheroids adapt to become hardier and more energy-efficient, and hence more resistant to today’s clinical treatments.

Joe Grieco, a fourth-year Virginia Tech translational biology, medicine, and health (TBMH) graduate student, wants to find a way to halt the cancer’s spread by manipulating the cells’ ability to adapt their metabolic activity. Grieco was awarded a National Institutes of Health’s Ruth L. Kirschstein Predoctoral Individual National Research Service Award to support his research in the Schmelz lab. The two-year grant is also supported by the National Cancer Institute.

"The more a cell can adapt to the conditions in a changing environment, the more aggressive it can be," said Schmelz, a professor in the Department of Human Nutrition, Foods, and Exercise in Virginia Tech's College of Agriculture and Life Sciences. "Identifying the molecular pathways for this adaptation can help us to design therapies to prevent deadly metastasis."

After ovarian cancer cells break off of the original mass, they migrate through the peritoneal cavity, a membrane-encased sac that holds abdominal organs in place, until they invade their first metastatic site: a fatty layer of tissue called the omentum. The peritoneal cavity lacks oxygen and nutrients, and yet the cancer cells adapt and thrive, especially when they clump together in spheroids.

Joe Grieco
Grieco in the Schmelz Lab at Virginia Tech

Grieco studies how the cells’ energy hubs, the mitochondria, adapt in this harsh environment. Initially the cells’ mitochondria become more fragmented. While this fragmentation impairs overall energy production, it also helps the cells survive under stress by preserving energy and regulating localized signaling to repair damage or remove damaged mitochondria. But Grieco observed that when the cells aggregate into spheroids and move into the peritoneal cavity, their mitochondria change.

"The original cells in the spheroid’s core have more mitochondrial fragmentation, whereas the outer layers become more metabolically active to support rapid tumor growth," Grieco said.

These mitochondrial adaptations happen quickly. But Grieco believes they can be stopped.

"Our goal is to find the molecular and cellular events that regulate these mitochondrial adaptations so we can intervene and suppress metastasis," Grieco said.

One drug that Grieco is studying, the antibiotic tigecycline, could inhibit ovarian cancer cells from producing the proteins needed to boost mitochondrial activity.

Over the next two years, Grieco will continue studying this drug’s potential, as well as shifts in mitochondrial activity as the disease progresses under different environmental conditions.

Grieco, who joined the Schmelz lab in 2018, has been interested in pursuing cancer research since his aunt passed away from metastatic lung cancer nearly a decade ago. Before joining the TBMH graduate program at Virginia Tech, he earned a bachelor’s degree in molecular genetics at the State University of New York–Fredonia.

For Grieco, this award is about more than just the funding.

"This NIH award really made me reconsider my career path. Initially as a graduate student, I thought I would finish my doctorate and go into industry to study cancer therapeutics, but now I know that I want to ask my own research questions, and I am motivated to pursue a career in academic research," Grieco said.