ArticleOncotarget2017
Induction of hypoxia and necrosis in multicellular tumor spheroids is associated with resistance to chemotherapy treatment.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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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
142 citing papers in PubMed, 267 citations in OpenAlex.
- High-content morphological profiling by Cell Painting in 3D spheroids.Nature communications · 2026Article
- Establishment of a Three-Dimensional In Vitro Model of Taste Bud Cells for Fat Taste Investigation.International journal of molecular sciences · 2026Article
- Comparative In Vitro Apoptotic Activity of Two Chimeric Anti-CD99 Antibodies Recognizing Distinct CD99 Regions in T-ALL Models.Biomedicines · 2026Article
- Matrix Stiffness Modulates 3D Spheroid-Derived Extracellular Vesicle Profiles and Discovery of Piezo1 Cargo.Cellular and molecular bioengineering · 2026Article
- Next-generation models for lymphoid malignancies: the rise of 3D culture systems in translational hematology.British journal of cancer · 2026Review
- Experimental workflow to evaluate nanoparticles combined with photon and carbon-ion medical irradiations in spheroids.Discover nano · 2026Article
- Can Complex 3D Models Effectively Replace 2D and Animal Models to Investigate the Microbe-Tumor-Immune Axis in Pancreatic Cancer Studies?Nutrients · 2026Review
- A Microwell Array Embedded Microfluidic Gradient Platform for Drug Screening on Tumor Spheroids.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Methodological innovations in perfusable vascular networks: Advancing high-density tissue models.Regenerative therapy · 2026Article
- New hybrid pyridine-1,2,4-triazole scaffolds: synthesis, in vitro evaluation of anticancer and antimicrobial activity, and in silico insights.Scientific reports · 2026Article
- Aquaporin-3 and aquaporin-5 impact the development of pancreatic ductal adenocarcinoma spheroids.FEBS open bio · 2026Article
- Measuring Propidium Iodide Brightness as a Function of Viability: A High-Throughput Quantitative Assessment of Hepatic Spheroids.Artificial organs · 2026Article
- Tumor organoids modeling reveals timed responses and interplay of radiotherapy and chemotherapy in pancreatic cancer.Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology · 2026Article
- Targeting pH regulation in cancer: combined mild alkaline treatment and NHE1 inhibition as a potential therapy for clear cell renal cell carcinoma.Molecular and cellular biochemistry · 2026Article
- Mechanochemical regulation of organoid morphogenesis: Integrated signaling circuits in engineered microenvironments.Materials today. Bio · 2026Review
- Establishment of a 3D Multicellular HCC Tumor Spheroid Model to Unravel Nrf2's Influence on the Tumor Immune Microenvironment.Bioengineering (Basel, Switzerland) · 2026Article
- Hypoxia-induced drug-resistance bias 3D cancer spheroid drug screens.APL bioengineering · 2026Article
- Coupling intraoperative bioprinting and surgical micropuncture for synergistic scaffold vascularization.Biomaterials · 2026Article
- Patient-Derived Models of Liver Cancer to Inform Clinical Treatment Paradigms: Recent Updates.Seminars in liver disease · 2026Review
- The application of experimental models for the drug discovery for digestive tumors.Molecular cancer · 2026Review
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Culture of cancerous cells in standard monolayer conditions poorly mirrors growth in three-dimensional architectures typically observed in a wide majority of cancers of different histological origin. Multicellular tumor spheroid (MCTS) culture models were developed to mimic these features. However, in vivo tumor growth is also characterized by the presence of ischemic and necrotic areas generated by oxygenation gradients and differential access to nutrients. Hypoxia and necrosis play key roles in tumor progression and resistance to treatment. To provide in vitro models recapitulating these events in highly controlled and standardized conditions, we have generated colorectal cancer (CRC) cell spheroids of different sizes and analyzed their gene expression profiles and sensitivity to treatment with 5FU, currently used in therapeutic protocols. Here we identify three MCTS stages, corresponding to defined spheroid sizes, characterized by normoxia, hypoxia, and hypoxia plus necrosis, respectively. Importantly, we show that MCTS including both hypoxic and necrotic areas most closely mimic gene expression profiles of in vivo-developing tumors and display the highest resistance to 5FU. Taken together, our data indicate that MCTS may mimic in vitro generation of ischemic and necrotic areas in highly standardized and controlled conditions, thereby qualifying as relevant models for drug screening purposes.
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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.