ArticlePLoS genetics2019
Heterogeneous pathway activation and drug response modelled in colorectal-tumor-derived 3D cultures.
Article in PLoS genetics, 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 51 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
51 citing papers in PubMed, 81 citations in OpenAlex.
- Immune and Immune-Integrated Organoids as NextGeneration Platforms for Disease Modeling.MedComm · 2025Review
- Wide-Field Optical Redox Imaging with Leading-Edge Detection Enables Assessment of Treatment Response and Heterogeneity in Patient-Derived Cancer Organoids.Cancer research · 2025Article
- Patient-Derived Organoid Biobanks for Translational Research and Precision Medicine: Challenges and Future Perspectives.Journal of personalized medicine · 2025Review
- Deciphering Breast Tumor Heterogeneity Through Patient-Derived Organoids and Circulating Tumor Cells.Journal of personalized medicine · 2025Review
- 3D tumor cultures for drug resistance and screening development in clinical applications.Molecular cancer · 2025Review
- Harnessing p53 for targeted cancer therapy: new advances and future directions.Transcription · 2025Review
- Spatial deconvolution from bulk DNA methylation profiles determines intratumoral epigenetic heterogeneity.Cell & bioscience · 2025Article
- High Efficiency Lentiviral Transduction of Colon Organoids Using Reversible 2D/3D Culture Techniques.Methods in molecular biology (Clifton, N.J.) · 2025Article
- XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients.Nature communications · 2024Article
- Integration of pan-omics technologies and three-dimensional in vitro tumor models: an approach toward drug discovery and precision medicine.Molecular cancer · 2024Review
- Advances in the application of colorectal cancer organoids in precision medicine.Frontiers in oncology · 2024Review
- Patient-derived tumor models and their distinctive applications in personalized drug therapy.Mechanobiology in medicine · 2023Review
- Functional precision oncology using patient-derived assays: bridging genotype and phenotype.Nature reviews. Clinical oncology · 2023Review
- Patient-Derived Organoids from Locally Advanced Gastric Adenocarcinomas Can Predict Resistance to Neoadjuvant Chemotherapy.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2023Article
- Sunitinib efficacy with minimal toxicity in patient-derived retinoblastoma organoids.Journal of experimental & clinical cancer research : CR · 2023Article
- Development of bioinformatics and multi-omics analyses in organoids.BMB reports · 2023Review
- Tumor heterogeneity: preclinical models, emerging technologies, and future applications.Frontiers in oncology · 2023Review
- Organoids for Modeling (Colorectal) Cancer in a Dish.Cancers · 2022Review
- The pivotal application of patient-derived organoid biobanks for personalized treatment of gastrointestinal cancers.Biomarker research · 2022Review
- Immune organoids: from tumor modeling to precision oncology.Trends in cancer · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Organoid cultures derived from colorectal cancer (CRC) samples are increasingly used as preclinical models for studying tumor biology and the effects of targeted therapies under conditions capturing in vitro the genetic make-up of heterogeneous and even individual neoplasms. While 3D cultures are initiated from surgical specimens comprising multiple cell populations, the impact of tumor heterogeneity on drug effects in organoid cultures has not been addressed systematically. Here we have used a cohort of well-characterized CRC organoids to study the influence of tumor heterogeneity on the activity of the KRAS/MAPK-signaling pathway and the consequences of treatment by inhibitors targeting EGFR and downstream effectors. MAPK signaling, analyzed by targeted proteomics, shows unexpected heterogeneity irrespective of RAS mutations and is associated with variable responses to EGFR inhibition. In addition, we obtained evidence for intratumoral heterogeneity in drug response among parallel "sibling" 3D cultures established from a single KRAS-mutant CRC. Our results imply that separate testing of drug effects in multiple subpopulations may help to elucidate molecular correlates of tumor heterogeneity and to improve therapy response prediction in patients.
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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.