ArticleJournal of the National Cancer Institute2019
Systematic Identification of Druggable Epithelial-Stromal Crosstalk Signaling Networks in Ovarian Cancer.
Article in Journal of the National Cancer Institute, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- The Impact of Stroma Admixture on Molecular Subtypes and Prognostic Gene Signatures in Serous Ovarian Cancer.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2020Pooled it
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- Spatial Cross-talk Modeling of the Tumor Microenvironment Identifies CCR5-Mediated Glia-to-Glia Signaling as a Key Regulator of Brain Metastatic Progression.Cancer research · 2025Article
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- Article
- Three-dimensional in vitro models in head and neck cancer: current trends and applications.Medical oncology (Northwood, London, England) · 2025Review
- Mathematically mapping the network of cells in the tumor microenvironment.Cell reports methods · 2025Article
- Cancer-associated fibroblasts in ovarian cancer: research progress.Frontiers in oncology · 2025Review
- Artificial Intelligence-Powered Insights into Polyclonality and Tumor Evolution.Research (Washington, D.C.) · 2025Review
- Calcitriol ameliorates motor deficits and prolongs survival of Chrne-deficient mouse, a model for congenital myasthenic syndrome, by inducing Rspo2.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Article
- sc2MeNetDrug: A computational tool to uncover inter-cell signaling targets and identify relevant drugs based on single cell RNA-seq data.PLoS computational biology · 2024Article
- Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer-The Possibility or the Necessity?Journal of personalized medicine · 2023Review
- Large-scale analysis of cell-cell communication reveals angiogenin-dependent tumor progression in clear cell renal cell carcinoma.iScience · 2023Article
- Spatial Transcriptomics Depict Ligand-Receptor Cross-talk Heterogeneity at the Tumor-Stroma Interface in Long-Term Ovarian Cancer Survivors.Cancer research · 2023Article
- Complex Analysis of Single-Cell RNA Sequencing Data.Biochemistry. Biokhimiia · 2023Review
- Validation approaches for computational drug repurposing: a review.AMIA ... Annual Symposium proceedings. AMIA Symposium · 2023Review
- "DEPHENCE" system-a novel regimen of therapy that is urgently needed in the high-grade serous ovarian cancer-a focus on anti-cancer stem cell and anti-tumor microenvironment targeted therapies.Frontiers in oncology · 2023Review
Corrections and comments
- Erratum issuedCorrigendum.2018
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundBulk tumor tissue samples are used for generating gene expression profiles in most research studies, making it difficult to decipher the stroma-cancer crosstalk networks. In the present study, we describe the use of microdissected transcriptome profiles for the identification of cancer-stroma crosstalk networks with prognostic value, which presents a unique opportunity for developing new treatment strategies for ovarian cancer.
methodsTranscriptome profiles from microdissected ovarian cancer-associated fibroblasts (CAFs) and ovarian cancer cells from patients with high-grade serous ovarian cancer (n = 70) were used as input data for the computational systems biology program CCCExplorer to uncover crosstalk networks between various cell types within the tumor microenvironment. The crosstalk analysis results were subsequently used for discovery of new indications for old drugs in ovarian cancer by computational ranking of candidate agents. Survival analysis was performed on ovarian tumor-bearing Dicer/Pten double-knockout mice treated with calcitriol, a US Food and Drug Administration-approved agent that suppresses the Smad signaling cascade, or vehicle control (9-11 mice per group). All statistical tests were two-sided.
resultsActivation of TGF-β-dependent and TGF-β-independent Smad signaling was identified in a particular subtype of CAFs and was associated with poor patient survival (patients with higher levels of Smad-regulated gene expression by CAFs: median overall survival = 15 months, 95% confidence interval [CI] = 12.7 to 17.3 months; vs patients with lower levels of Smad-regulated gene expression: median overall survival = 26 months, 95% CI = 15.9 to 36.1 months, P = .02). In addition, the activated Smad signaling identified in CAFs was found to be targeted by repositioning calcitriol. Calcitriol suppressed Smad signaling in CAFs, inhibited tumor progression in mice, and prolonged the median survival duration of ovarian cancer-bearing mice from 36 to 48 weeks (P = .04).
conclusionsOur findings suggest the feasibility of using novel multicellular systems biology modeling to identify and repurpose known drugs targeting cancer-stroma crosstalk networks, potentially leading to faster and more effective cures for cancers.
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