ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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.
The trial behind it
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
17 citing papers in PubMed.
- Spop-binding bifunctional degraders: a novel approach for cancer immunotherapy.Journal of advanced research · 2026Article
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- Ubiquitin-centered post-translational modification crosstalk orchestrates tumor immunity and immunotherapy response.Experimental hematology & oncology · 2026Review
- Proanthocyanidins enhance antitumor immunity by promoting ubiquitin-proteasomal PD-L1 degradation via stabilization of LKB1 and SYVN1.The Journal of clinical investigation · 2026Article
- Integrated metabolomics and machine learning identify predictive biomarkers via SHAP analysis for sintilimab-induced rash in lung cancer patients.Frontiers in pharmacology · 2026Article
- Natural product FZJDXJ enhances CD8+ T-cell glycolysis to relieve exhaustion and augment antitumor immunity in HBVFrontiers in nutrition · 2026Article
- Traditional Chinese medicine as a potential barrier-oriented sensitization strategy for immune checkpoint blockade in microsatellite-stable colorectal cancer: from resistance mechanisms to translational validation.Frontiers in immunology · 2026Review
- Integrating chemokine signatures and multi-omic biomarkers to predict immunotherapy response in non-small cell lung cancer: a comprehensive narrative review.Frontiers in oncology · 2026Review
- IL-23 promotes PD-L1 expression and tumor immune evasion via METTL16 pathway.American journal of cancer research · 2026Article
- Exploring traditional Chinese medicine to enhance the efficacy and reduce toxicity of immunotherapy for non-small cell lung cancer from the perspective of "spleen deficiency": a trial protocol for mechanism and clinical evidence.Frontiers in oncology · 2026Article
- Comprehensive profiling of alternative splicing and immune landscapes in rectal cancer: implications for mRNA vaccine design and immune subtype stratification.Frontiers in oncology · 2026Article
- Targeting the akt/mtor signaling pathway by maprotiline leads to tumor suppression in T-cell lymphoma.Annals of hematology · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Targeting DNA Damage Response-Mediated Resistance in Non-Small Cell Lung Cancer: From Mechanistic Insights to Drug Development.Current oncology (Toronto, Ont.) · 2025Review
- Drug functional remapping: a new promise for tumor immunotherapy.Frontiers in oncology · 2025Review
- Network Medicine-Based Strategy Identifies Maprotiline as a Repurposable Drug by Inhibiting PD-L1 Expression via Targeting SPOP in Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrative Multi-Omics Analysis and Experimental Validation Identify SPOP as a Prognostic Biomarker and Immune Regulator in Lung Adenocarcinoma.Journal of Cancer · 2025Article
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Immune checkpoint inhibitors (ICIs) are drugs that inhibit immune checkpoint (ICP) molecules to restore the antitumor activity of immune cells and eliminate tumor cells. Due to the limitations and certain side effects of current ICIs, such as programmed death protein-1, programmed cell death-ligand 1, and cytotoxic T lymphocyte-associated antigen 4 (CTLA4) antibodies, there is an urgent need to find new drugs with ICP inhibitory effects. In this study, a network-based computational framework called multi-network algorithm-driven drug repositioning targeting ICP (Mnet-DRI) is developed to accurately repurpose novel ICIs from ≈3000 Food and Drug Administration-approved or investigational drugs. By applying Mnet-DRI to PD-L1, maprotiline (MAP), an antidepressant drug is repurposed, as a potential PD-L1 modifier for colorectal and lung cancers. Experimental validation revealed that MAP reduced PD-L1 expression by targeting E3 ubiquitin ligase speckle-type zinc finger structural protein (SPOP), and the combination of MAP and anti-CTLA4 in vivo significantly enhanced the antitumor effect, providing a new alternative for the clinical treatment of colorectal and lung cancer.
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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.