ArticlePloS one2020
Outgrowth of erlotinib-resistant subpopulations recapitulated in patient-derived lung tumor spheroids and organoids.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Lung Organoids: Systematic Review of Recent Advancements and its Future Perspectives.Tissue engineering and regenerative medicine · 2024Pooled it
- Patient-derived organoids in non-small cell lung cancer: advances in drug sensitivity testing.Frontiers in pharmacology · 2025Review
- Bridging the gap: how patient-derived lung cancer organoids are transforming personalized medicine.Frontiers in cell and developmental biology · 2025Review
- Extracellular Matrix Sulfation in the Tumor Microenvironment Stimulates Cancer Stemness and Invasiveness.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Ex vivo drug testing of patient-derived lung organoids to predict treatment responses for personalized medicine.Lung cancer (Amsterdam, Netherlands) · 2024Review
- 3D cell culture models in research: applications to lung cancer pharmacology.Frontiers in pharmacology · 2024Review
- The application of patient-derived organoid in the research of lung cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Review
- Functional precision oncology using patient-derived assays: bridging genotype and phenotype.Nature reviews. Clinical oncology · 2023Review
- The interplay of cells, polymers, and vascularization in three-dimensional lung models and their applications in COVID-19 research and therapy.Stem cell research & therapy · 2023Review
- Patient-derived spheroids and patient-derived organoids simulate evolutions of lung cancer.Heliyon · 2023Article
- Lung cancer organoids: models for preclinical research and precision medicine.Frontiers in oncology · 2023Review
- Organ-on-a-chip meets artificial intelligence in drug evaluation.Theranostics · 2023Review
- Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications.Frontiers in bioengineering and biotechnology · 2023Review
- Optimization of tumor spheroid model in mesothelioma and lung cancers and anti-cancer drug testing in H2052/484 spheroids.Oncotarget · 2021Article
- Biomedical Applications of Non-Small Cell Lung Cancer Spheroids.Frontiers in oncology · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A model that recapitulates development of acquired therapeutic resistance is needed to improve oncology drug development and patient outcomes. To achieve this end, we established methods for the preparation and growth of spheroids from primary human lung adenocarcinomas, including methods to culture, passage, monitor growth, and evaluate changes in mutational profile over time. Primary lung tumor spheroids were cultured in Matrigel® with varying concentrations of erlotinib, a small molecule kinase inhibitor of epidermal growth factor receptor (EGFR) that is ineffective against KRAS mutant cells. Subtle changes in spheroid size and number were observed within the first two weeks of culture. Spheroids were cultured for up to 24 weeks, during which time interactions between different cell types, movement, and assembly into heterogeneous organoid structures were documented. Allele-specific competitive blocker PCR (ACB-PCR) was used to quantify low frequency BRAF V600E, KRAS G12D, KRAS G12V, and PIK3CA H1047R mutant subpopulations in tumor tissue residue (TR) samples and cultured spheroids. Mutant subpopulations, including multiple mutant subpopulations, were quite prevalent. Twelve examples of mutant enrichment were found in eight of the 14 tumors analyzed, based on the criteria that a statistically-significant increase in mutant fraction was observed relative to both the TR and the no-erlotinib control. Of the mutants quantified in erlotinib-treated cultures, PIK3CA H1047 mutant subpopulations increased most often (5/14 tumors), which is consistent with clinical observations. Thus, this ex vivo lung tumor spheroid model replicates the cellular and mutational tumor heterogeneity of human lung adenocarcinomas and can be used to assess the outgrowth of mutant subpopulations. Spheroid cultures with characterized mutant subpopulations could be used to investigate the efficacy of lung cancer combination therapies.
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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.