ArticleNature cancer2022
Functional patient-derived organoid screenings identify MCLA-158 as a therapeutic EGFR × LGR5 bispecific antibody with efficacy in epithelial tumors.
Article in Nature cancer, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers, 1 of them a synthesis that pooled it.
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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
95 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- Applications of lung cancer organoids in precision medicine: from bench to bedside.Cell communication and signaling : CCS · 2023Pooled it
- Stemness in Colon Cancer.Methods in molecular biology (Clifton, N.J.) · 2027Article
- The transformative impact of stem cell core facilities in biomedical research.Stem cell reports · 2026Review
- Advances in Bispecific Antibodies and Antibody-Drug Conjugates for Colorectal Cancer Treatment.Antibodies (Basel, Switzerland) · 2026Review
- Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates.Acta pharmaceutica Sinica. B · 2026Review
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
- LGR5: from stem cell marker to therapeutic target.Trends in cancer · 2026Review
- Organoids, organ-on-a-chip, and microtumors: Biomimetic 3D tumor models advancing drug development and precision medicine.Acta pharmaceutica Sinica. B · 2026Review
- Disrupting MED8-dependent epigenetic reprogramming augments avapritinib sensitivity in PDGFRA-driven glioma.Journal of experimental & clinical cancer research : CR · 2026Article
- Organoid models: Regulations and prospects for the development of investigational new drugs.Chinese medical journal · 2026Review
- Intestinal Organoid-Based Mathematical Modeling Predicts Clinical Gastrointestinal Toxicity of Oral Oncology Drugs.CPT: pharmacometrics & systems pharmacology · 2026Article
- Reimagining human-centric drug development with new approach methodologies.Science (New York, N.Y.) · 2026Review
- Harnessing Tumor Organoids to Revolutionize Immunotherapy Research.Cancer medicine · 2026Review
- Human organoids as 3D in vitro platforms for drug discovery: opportunities and challenges.Nature reviews. Drug discovery · 2026Review
- The application of experimental models for the drug discovery for digestive tumors.Molecular cancer · 2026Review
- A Plastic EMP1+ to LGR5+ Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Patient-derived tumor organoids for new drug development: promises and challenges.Investigational new drugs · 2026Review
- MAPK-driven epithelial cell plasticity drives colorectal cancer therapeutic resistance.Nature · 2026Article
- Global scientific trends in organoids from 2000 to 2024: a data-driven bibliometric and visualized analysis.International journal of surgery (London, England) · 2026Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
39 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Patient-derived organoids (PDOs) recapitulate tumor architecture, contain cancer stem cells and have predictive value supporting personalized medicine. Here we describe a large-scale functional screen of dual-targeting bispecific antibodies (bAbs) on a heterogeneous colorectal cancer PDO biobank and paired healthy colonic mucosa samples. More than 500 therapeutic bAbs generated against Wingless-related integration site (WNT) and receptor tyrosine kinase (RTK) targets were functionally evaluated by high-content imaging to capture the complexity of PDO responses. Our drug discovery strategy resulted in the generation of MCLA-158, a bAb that specifically triggers epidermal growth factor receptor degradation in leucine-rich repeat-containing G-protein-coupled receptor 5-positive (LGR5+) cancer stem cells but shows minimal toxicity toward healthy LGR5+ colon stem cells. MCLA-158 exhibits therapeutic properties such as growth inhibition of KRAS-mutant colorectal cancers, blockade of metastasis initiation and suppression of tumor outgrowth in preclinical models for several epithelial cancer types.
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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.