ArticleScience translational medicine2020
Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 80 citations in OpenAlex.
- Plasticity of Non-Apoptotic Residual Tumor Cells After Neoadjuvant Immunochemotherapy: Epigenetic and Microenvironmental Determinants.Biomolecules · 2026Review
- A high-MAPK, low-WNT cell state drives metastatic dissemination in colorectal cancer.Nature cancer · 2026Article
- LGR5: from stem cell marker to therapeutic target.Trends in cancer · 2026Review
- Efficacy of dual KRASCell death & disease · 2026Article
- Dormancy in Metastatic Colorectal Cancer: Tissue Engineering Opportunities forTissue engineering. Part B, Reviews · 2026Review
- The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer.Cancer discovery · 2026Article
- Decellularized Extracellular Matrix Scaffolds to Engineer the Dormant Landscape of Microscopic Colorectal Cancer Liver Metastasis.Advanced healthcare materials · 2026Article
- Paneth-like transition drives resistance to dual targeting of KRAS and EGFR in colorectal cancer.Cancer cell · 2026Article
- Targeting Drug-Tolerant Persister Cancer Cells: Can Nanomaterial-Based Strategies Be Helpful for Anti-DTP Therapies?Pharmaceutics · 2025Review
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.Cell reports. Medicine · 2025Article
- Longitudinal single-cell analysis of glucagon-like peptide-2 treatment in patients with short bowel syndrome.JCI insight · 2025Article
- Epigenetic Heritability of Cell Plasticity Drives Cancer Drug Resistance through a One-to-Many Genotype-to-Phenotype Paradigm.Cancer research · 2025Article
- LiGeR-HN phase III trials of petosemtamab + pembrolizumab and petosemtamab monotherapy in recurrent or metastatic HNSCC.Future oncology (London, England) · 2025Article
- Cetuximab increases LGR5 expression and augments LGR5-targeting antibody-drug conjugate efficacy in patient-derived colorectal cancer models.bioRxiv : the preprint server for biology · 2025Article
- Review
- PDX models for functional precision oncology and discovery science.Nature reviews. Cancer · 2025Review
- Sustained Endocytosis Inhibition via Locally-Injected Drug-Eluting Hydrogel Improves ADCC-Mediated Antibody Therapy in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts.Nature communications · 2024Article
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Mechanisms of metastatic colorectal cancer.Nature reviews. Gastroenterology & hepatology · 2024Review
Corrections and comments
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Authors and funding
32 authors at 7 institutions in 4 countries.
Funding
Abstract
Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to therapy, leading to relapse. Using patient-derived xenografts (PDXs), we observed that mCRC cells surviving EGFR inhibition exhibited gene expression patterns similar to those of a quiescent subpopulation of normal intestinal secretory precursors with Paneth cell characteristics. Compared with untreated tumors, these pseudodifferentiated tumor remnants had reduced expression of genes encoding EGFR-activating ligands, enhanced activity of human epidermal growth factor receptor 2 (HER2) and HER3, and persistent signaling along the phosphatidylinositol 3-kinase (PI3K) pathway. Clinically, properties of residual disease cells from the PDX models were detected in lingering tumors of responsive patients and in tumors of individuals who had experienced early recurrence. Mechanistically, residual tumor reprogramming after EGFR neutralization was mediated by inactivation of Yes-associated protein (YAP), a master regulator of intestinal epithelium recovery from injury. In preclinical trials, Pan-HER antibodies minimized residual disease, blunted PI3K signaling, and induced long-term tumor control after treatment discontinuation. We found that tolerance to EGFR inhibition is characterized by inactivation of an intrinsic lineage program that drives both regenerative signaling during intestinal repair and EGFR-dependent tumorigenesis. Thus, our results shed light on CRC lineage plasticity as an adaptive escape mechanism from EGFR-targeted therapy and suggest opportunities to preemptively target residual disease.
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