Molecular Mapping Sheds Light on How Benign Borderline Ovarian Tumors Turn Invasive

Recent advances in spatial proteomics have provided new insights into the progression of ovarian tumors, particularly low-grade serous ovarian cancer (LGSC), which comprises about 5% to 10% of epithelial ovarian cancers. Often starting as non-invasive lesions known as serous borderline tumors, these tumors can sometimes evolve into invasive, life-threatening disease. Although traditional management with surgery is effective in many cases, some tumors recur as aggressive LGSC, and the underlying mechanisms remain poorly understood.

Led by researchers from the Max Planck Society and experts like Ernst Lengyel, the study aimed to map the detailed molecular landscape of these tumors at different stages. Using high-precision laser microdissection, tissue samples from patients were carefully analyzed to distinguish tumor cells from their microenvironment. Advanced machine learning algorithms and mass spectrometry then generated specific protein signatures for each cell type, creating comprehensive molecular maps.

This innovative approach, called Deep Visual Proteomics, allowed scientists to visualize thousands of proteins within tumor tissues at single-cell resolution. By combining spatial protein analysis with RNA data, researchers identified critical signaling pathways involved in tumor progression. Notably, they discovered early signs of malignant transformation in intermediate-stage tumors called micropapillary tumors and pinpointed proteins that might act as molecular switches driving invasion.

One key finding was the identification of proteins typically associated with the central nervous system, such as NOVA2, which was exclusively present in invasive tumor forms and metastases. Experimental removal of these proteins in cell cultures affected tumor growth and invasion, suggesting they could be targets for future therapies.

The study also explored new therapeutic strategies. By analyzing their spatial maps, scientists identified 16 potential drug targets and tested a combination therapy in preclinical models. The pairing of Milciclib — an inhibitor of cell proliferation — with Mirvetuximab, which delivers targeted toxins to FOLR1-expressing cells, showed promising results in reducing tumor burden, opening new avenues for treating chemo-resistant LGSC.

While more research is necessary to confirm safety and effectiveness in humans, this work demonstrates the potential of spatial proteomics to uncover the molecular dynamics of tumor evolution. Such insights could lead to personalized treatments that target specific vulnerabilities within ovarian tumors, ultimately improving patient outcomes.

This groundbreaking research underscores the importance of advanced molecular mapping techniques in understanding cancer progression and developing targeted therapies. It highlights the transformative potential of spatial omics to decode complex disease ecosystems and guide precision medicine approaches.