ArticleProceedings of the National Academy of Sciences of the United States of America2016
Rapid emergence and mechanisms of resistance by U87 glioblastoma cells to doxorubicin in an in vitro tumor microfluidic ecology.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- Decoding Viral Transmission Dynamics in Structured Populations Using a Microfluidic Herd-Immunity-on-a-Chip Platform.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Dual-targeted glutathione-glutamate functionalized Bismuth-Niosomes hybrid nanosystem for co-delivery of doxorubicin and Pi3K inhibitor into U87 glioblastoma cells.Scientific reports · 2026Article
- Loss of TRPV1 may shift capsaicin response from MAPK-CASC11-MYC protection to mitochondrial apoptosis in glioblastoma U87 cells.International journal of biological macromolecules · 2026Article
- Bio-Assisted Synthesis of Reduced Graphene Oxide Nanosheets From Graphene Oxide: Promising and Efficient Cytotoxic and Antidiabetic Potency in In Vitro, Kinetic, and In Silico Models.International journal of biomaterials · 2026Article
- Enhancing ferroptosis and inhibiting ABCB1 make the novel aldose reductase inhibitor 5F-E a promising sensitizer in liver cancer.Pharmaceutical science advances · 2025Article
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- Exploring the heterogeneity in glioblastoma cellular mechanics using in-vitro assays and atomic force microscopy.Scientific reports · 2025Article
- Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress.Journal of translational medicine · 2024Article
- Modeling of brain tumors usingHeliyon · 2024Review
- Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.Sensors (Basel, Switzerland) · 2024Review
- Article
- Preclinical Models and Technologies in Glioblastoma Research: Evolution, Current State, and Future Avenues.International journal of molecular sciences · 2023Review
- Biomaterial-basedCancer pathogenesis and therapy · 2023Review
- Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer.Cancers · 2023Article
- In Vitro Tumor Models on Chip and Integrated Microphysiological Analysis Platform (MAP) for Life Sciences and High-Throughput Drug Screening.Biosensors · 2023Review
- Strategies for developing complex multi-component in vitro tumor models: Highlights in glioblastoma.Advanced drug delivery reviews · 2022Review
- Optimizing the Design of Blood-Brain Barrier-Penetrating Polymer-Lipid-Hybrid Nanoparticles for Delivering Anticancer Drugs to Glioblastoma.Pharmaceutical research · 2021Article
- Systematic analysis of potential targets of the curcumin analog pentagamavunon-1 (PGV-1) in overcoming resistance of glioblastoma cells to bevacizumab.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2021Article
- NSD1: A Lysine Methyltransferase between Developmental Disorders and Cancer.Life (Basel, Switzerland) · 2021Review
- Microengineered 3D Tumor Models for Anti-Cancer Drug Discovery in Female-Related Cancers.Annals of biomedical engineering · 2021Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vitro prediction of the probable rapid emergence of resistance to a drug in tumors could act to winnow out potential candidates for further costly development. We have developed a microfluidic device consisting of ∼500 hexagonal microcompartments that provides a complex ecology with wide ranges of drug and nutrient gradients and local populations. This ecology of a fragmented metapopulation induced the drug resistance in stage IV U87 glioblastoma cells to doxorubicin in 7 d. Exome and transcriptome sequencing of the resistant cells identified mutations and differentially expressed genes. Gene ontology and pathway analyses of the genes identified showed that they were functionally relevant to the established mechanisms of doxorubicin action. Specifically, we identified (i) a frame-shift insertion in the filamin-A gene, which regulates the influx and efflux of topoisomerase II poisons; (ii) the overexpression of aldo-keto reductase enzymes, which convert doxorubicin into doxorubicinol; and (iii) activation of NF-κB via alterations in the nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway from mutations in three genes (CARD6, NSD1, and NLRP13) and the overexpression of inflammatory cytokines. Functional experiments support the in silico analyses and, together, demonstrate the effects of these genetic changes. Our findings suggest that, given the rapid evolution of resistance and the focused response, this technology could act as a rapid screening modality for genetic aberrations leading to resistance to chemotherapy as well as counter selection of drugs unlikely to be successful ultimately.
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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.