A team of researchers from the Department of Obstetrics and Gynecology at the University of Chicago and the Max Planck Institute of Biochemistry in Germany made a significant breakthrough in understanding low-grade serous ovarian cancer (LGSC)—a slow-growing but stubborn cancer that affects mostly younger women and is not responsive to chemotherapy.
Using a new technique called Deep Visual Proteomics, the researchers created detailed protein maps of tissue samples from patients at different disease stages, from benign serous borderline tumors to invasive low-grade ovarian cancers. By combining this protein mapping with advanced spatial RNA analysis, they discovered how harmless ovarian tumors can become invasive and threatening.
Notably, the researchers also found a protein called NOVA2, which is not present in benign tumors, but is found in invasive cancers. This protein may help trigger this dangerous transformation. The research was published today in Cancer Cell.
“By profiling the disease at high spatial resolution, we could trace how these tumors evolve along a gradient of malignancy and interact with their environment,” said Lisa Schweizer, PhD, first author and clinical scientist at the Max Planck Institute. Schweizer works in the research group of Professor Matthias Mann, PhD, co-lead author of this study.
Current treatments for LGSC are limited because the cancer tends to spread slowly and doesn’t respond well to chemotherapy. By studying patient tissues and human cell models, the team showed that removing specific proteins could reduce the ability of cancer cells to invade healthy tissue.
The group also identified 16 possible drug targets and tested a new combination therapy—Milciclib and Mirvetuximab—which greatly reduced tumor growth in mouse models, laying the groundwork for future patient trials.
“From the beginning, we intended to draw an unbiased map of how low-grade serous tumors of the ovary evolve to uncover better treatment targets,” said Ernst Lengyel, MD PhD, Arthur L. and Lee G. Herbst Distinguished Service Professor and Chair of Obstetrics and Gynecology at UChicago. Lengyel is the senior author of the study and a leading ovarian cancer expert in the Section of Gynecologic Oncology at UChicago.
The research was conducted by an international team led by Lengyel and Mann, with contributions from scientists and clinicians from both institutions. While further studies are needed, the discovery brings hope for more effective, targeted treatments for women with this challenging cancer. More broadly, it demonstrates how advanced spatial mapping technologies can revolutionize cancer research and treatment.
“This work shows the power of collaboration in developing new therapies for difficult diseases,” Lengyel said.
Adapted from a press release provided by the Max Planck Institute of Biochemistry.
