Most women with metastatic ovarian cancer have a survival rate of less than five years. Researchers at the University of Pittsburgh Swanson School of Engineering are working to change that.

Ioannis Zervantonakis, assistant professor of bioengineering at Pete, and his team received $792,000 for four years from the American Cancer Society to understand the biology behind the cell interactions that cause ovarian cancer to spread to other parts of the body.

To prevent ovarian cancer from spreading throughout the abdomen, patients are treated with a combination of surgery and chemotherapy; However, the prognosis remains bleak.

Because ovarian cancer is diagnosed at a late stage, patients usually do not respond to chemotherapy. There is an urgent need to understand how ovarian cancer progresses and to develop better bioengineering models that can help researchers discover new therapeutic targets.”

Ioannis Zervantonakis, Assistant Professor of Bioengineering, University of Pittsburgh Swanson School of Engineering

Ovarian cancer becomes metastatic when tumors form from attachments and growths on the epithelial cells or cells that cover the outer surface of the internal organs in the abdominal cavity. In most cases, these attachments result in complete invasion of the host tissue, which greatly reduces the patient’s chance of surviving previous treatment.

Cancer cells secrete IGFBP2, a protein associated with a worse prognosis for patients. When IGFBP2 binds to epithelial cells, it results in activation of the SRC pathway, which supports metastatic progression. The team believes that by targeting the IGFBP2-SRC interaction between cancer cells and epithelial cells, ovarian cancer metastasis can be halted.

By developing new 3D models using microfluidic technology (manipulating fluid motion at the micron scale), the team will be able to study how IGFBP2 production by cancer cells affects epithelial cell biology and pro-metastasis functions.

“Most of our experiments will be done in 3D microfluidics or mouse models to give us a really good idea of ​​what really happens when cells talk to each other through the production of IGFBP2,” said Dorota Jaswinska, a graduate student at Beth who is leading the experimental trial. Work at Zervantonakis Lab on the project.

Since this project targets epithelial cells in the abdominal cavity, it will eventually be applied to other cancers that colonize the abdominal organs.

The grant is expected to begin in January 2023. In another project on ovarian cancer metastasis, Zervantonakis received $160,000 from the Elsa Pardee Foundation in 2020 to study the role of macrophages in metastatic ovarian cancer.

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