ArticleScience advances2023
Small-molecule PIK-93 modulates the tumor microenvironment to improve immune checkpoint blockade response.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 33 citations in OpenAlex.
- Ubiquitin-driven regulation of immune checkpoints in lung cancer: Mechanisms and therapeutic implications (Review).Experimental and therapeutic medicine · 2026Review
- Co-stimulatory signal deficiency impairs cytotoxic T lymphocyte function in tumor immune evasion: molecular mechanisms and therapeutic implications.Journal of translational medicine · 2026Review
- Approaches to visualize, quantify, and manipulate phosphoinositides in cells.Histochemistry and cell biology · 2026Review
- Multiplex networks-based directed graph neural network for cancer driver gene identification.PLoS computational biology · 2026Article
- SLC25A39 Upregulation Is Associated with DNA Methylation, Immune Cell Infiltration, and Poor Prognosis in Hepatocellular Carcinoma.International journal of molecular sciences · 2026Article
- PIK3R1 as a Gastric Cancer Biomarker Linked to CD73Oncology research · 2026Article
- Integrating artificial intelligence into small molecule development for precision cancer immunomodulation therapy.npj drug discovery · 2025Review
- Phosphoproteomic and Acetylomic Characterization of Colorectal Cancer Cells Treated with Kinase Inhibitors.ACS pharmacology & translational science · 2025Article
- ImmuProgML: machine learning-based dissection of cancer-immune dynamics during tumor progression to improve immunotherapy.Journal of translational medicine · 2025Article
- Post-translational modifications of cancer immune checkpoints: mechanisms and therapeutic strategies.Molecular cancer · 2025Review
- Deep graph convolutional network-based multi-omics integration for cancer driver gene identification.Briefings in bioinformatics · 2025Article
- Advances in cancer immunotherapy: historical perspectives, current developments, and future directions.Molecular cancer · 2025Review
- Inositol metabolism as a broad-spectrum antiviral target.Frontiers in microbiology · 2025Review
- Identification of glucocorticoid-related genes in systemic lupus erythematosus using bioinformatics analysis and machine learning.PloS one · 2025Article
- Regulation and Crosstalk of Cells and Factors in the Pancreatic Cancer Microenvironment.Current cancer drug targets · 2025Review
- Covalent organic frameworks for cancer immunotherapy: mechanisms, applications, and prospects.Frontiers in immunology · 2025Review
- Systematic pan-cancer analysis identifies ZBTB11 as a potential pan-cancer biomarker and immunotherapy target in multiple tumor types.Discover oncology · 2024Article
- Towards simplified graph neural networks for identifying cancer driver genes in heterophilic networks.Briefings in bioinformatics · 2024Article
- Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.Experimental hematology & oncology · 2024Review
- Glucocorticoids in lung cancer: Navigating the balance between immunosuppression and therapeutic efficacy.Heliyon · 2024Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) targeting PD-L1 immunotherapy are state-of-the-art treatments for advanced non-small cell lung cancer (NSCLC). However, the treatment response of certain patients with NSCLC is unsatisfactory because of an unfavorable tumor microenvironment (TME) and poor permeability of antibody-based ICIs. In this study, we aimed to discover small-molecule drugs that can modulate the TME to enhance ICI treatment efficacy in NSCLC in vitro and in vivo. We identified a PD-L1 protein-modulating small molecule, PIK-93, using a cell-based global protein stability (GPS) screening system. PIK-93 mediated PD-L1 ubiquitination by enhancing the PD-L1-Cullin-4A interaction. PIK-93 reduced PD-L1 levels on M1 macrophages and enhanced M1 antitumor cytotoxicity. Combined PIK-93 and anti-PD-L1 antibody treatment enhanced T cell activation, inhibited tumor growth, and increased tumor-infiltrating lymphocyte (TIL) recruitment in syngeneic and human peripheral blood mononuclear cell (PBMC) line-derived xenograft mouse models. PIK-93 facilitates a treatment-favorable TME when combined with anti-PD-L1 antibodies, thereby enhancing PD-1/PD-L1 blockade cancer immunotherapy.
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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.