ArticleCancer discovery2025
Aged and BRCA-Mutated Stromal Cells Drive Epithelial Cell Transformation.
Article in Cancer discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed.
- Rethinking ovarian cancer III: the past decade and future directions.Nature reviews. Cancer · 2026Review
- Sequential platinum and PARP Inhibition enhances PD1 immunotherapy efficacy in murine Brca2 mutated pancreatic cancer.Scientific reports · 2026Article
- Distinct origins of high-grade serous ovarian carcinoma: genetic and epigenetic evidence linking ovarian and fallopian tube epithelium to clinical outcomes and early detection.Molecular biology reports · 2025Review
- Integrative machine learning-driven prognosis and immunotherapy stratification via lactylation-associated gene in ovarian cancer.NPJ precision oncology · 2025Article
- Integration of cell-type resolved spatial proteomics and transcriptomics reveals novel mechanisms in early ovarian cancer.medRxiv : the preprint server for health sciences · 2025Article
Corrections and comments
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Authors and funding
23 authors.
Funding
Abstract
The fundamental steps in high-grade serous ovarian cancer (HGSOC) initiation are unclear, presenting critical barriers to the prevention and early detection of this deadly disease. Current models propose that fallopian tube epithelial (FTE) cells transform into serous tubal intraepithelial carcinoma (STIC) precursor lesions and subsequently into HGSOC. In this study, we report that an epigenetically altered mesenchymal stem cell niche, termed high-risk mesenchymal stromal/stem cell (hrMSC), exists prior to STIC lesion formation. hrMSCs are enriched in STIC stroma and contribute to a stromal "field effect" extending beyond the borders of the STIC lesion. hrMSCs promote DNA damage in FTE cells while also fostering FTE cell survival. hrMSCs induce malignant transformation of the FTE, resulting in metastatic cancer in vivo, indicating that hrMSCs promote cancer initiation. hrMSCs are significantly enriched in BRCA1/2 mutation carriers and increase with age. Combined, these findings indicate that hrMSCs can incite ovarian cancer initiation and have important implications for ovarian cancer detection and prevention. SIGNIFICANCE: This work demonstrates a critical role of fallopian tube stromal cells in HGSOC initiation with implications for the pathophysiology of HGSOC formation and the development of prevention and early detection strategies critically needed in this disease. Additionally, the identification of stromal-mediated epithelial transformation has broad implications for understanding pan-cancer initiation. See related commentary by Recouvreux and Orsulic, p. 1093.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.