卵巣がんの浸潤化に関する新知見を発表(New approaches for the treatment of ovarian cancer)

2025-06-26 マックス・プランク研究所

The female reproductive system as focus of this study in the background of a serous Borderline tumor. In this microscopy image, cells have been stained using immunofluorescence. Single cells of the tumor can be recognized by an artificial intelligence algorithm (yellow).
© Photo: Lisa Schweizer, MPI of Biochemistry

<関連情報>

• https://www.mpg.de/24969156/0626-bioc-when-tumors-turn-invasive-new-research-on-ovarian-cancer-153945-x1
• https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00253-3

空間的プロテオ・トランスクリプトーム・プロファイリングが明らかにする境界卵巣腫瘍とその浸潤進展の分子景観 Spatial proteo-transcriptomic profiling reveals the molecular landscape of borderline ovarian tumors and their invasive progression

Lisa Schweizer ∙ Hilary A. Kenny ∙ Rahul Krishnan ∙ … ∙ Ricardo R. Lastra ∙ Matthias Mann
Cancer Cell  Published:June 26, 2025
DOI:https://doi.org/10.1016/j.ccell.2025.06.004

Highlights

• Integration of cell-type resolved spatial proteomics and transcriptomics
• Tumor progression from borderline ovarian tumors to metastatic low-grade serous cancer
• Micropapillary borderline tumors are an intermediate stage to low-grade ovarian cancer
• Mechanistic evidence supporting new combination treatments for low-grade ovarian cancer

Summary

Epithelial serous borderline tumors (SBT) are non-invasive neoplastic ovarian lesions that may recur as chemo-resistant low-grade serous cancer (LGSC). While genetic alterations suggest a common origin, the transition from SBT to LGSC remains poorly understood. Here, we integrate cell-type resolved spatial proteomics and transcriptomics to elucidate the evolution from SBT to LGSC and its corresponding metastases in both stroma and tumor. The transition occurs within the epithelial compartment through an intermediary stage with micropapillary features, during which LGSC overexpresses c-Met and several brain-specific proteins. Within the tumor microenvironment, interconnectivity between cancer and stromal cells, along with enzymes degrading a packed extracellular matrix, suggests functional collaboration among various cell types. We functionally validated 16 drug targets identified through integrated spatial transcriptomics and proteomics. Combined treatment targeting CDK4/6 (milciclib) and FOLR1 (mirvetuximab) achieved significant tumor reduction in vivo, representing a promising therapeutic strategy for LGSC.