ArticleScience translational medicine2014
Single-cell pharmacokinetic imaging reveals a therapeutic strategy to overcome drug resistance to the microtubule inhibitor eribulin.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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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.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
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- Supercontinuum-tailoring multicolor imaging reveals spatiotemporal dynamics of heterogeneous tumor evolution.Nature communications · 2024Article
- Immunomodulatory Effects of Halichondrin Isolated from Marine Sponges and Its Synthetic Analogs in Oncological Applications.Marine drugs · 2024Review
- Pharmacological Polarization of Tumor-Associated Macrophages Toward a CXCL9 Antitumor Phenotype.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A non-lipid nucleic acid delivery vector with dendritic cell tropism and stimulation.Theranostics · 2024Article
- Integrating inverse reinforcement learning into data-driven mechanistic computational models: a novel paradigm to decode cancer cell heterogeneity.Frontiers in systems biology · 2024Article
- Single-Cell Proliferation Microfluidic Device for High Throughput Investigation of Replicative Potential and Drug Resistance of Cancer Cells.Cellular and molecular bioengineering · 2023Article
- Perfusion Window Chambers Enable Interventional Analyses of Tumor Microenvironments.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Multidimensional Imaging of Breast Cancer.Cold Spring Harbor perspectives in medicine · 2023Review
- Intravital imaging to study cancer progression and metastasis.Nature reviews. Cancer · 2023Review
- Multinuclear MRI in Drug Discovery.Molecules (Basel, Switzerland) · 2022Review
- New and Emerging Research on Solute Carrier and ATP Binding Cassette Transporters in Drug Discovery and Development: Outlook From the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Spatial analysis of drug absorption, distribution, metabolism, and toxicology using mass spectrometry imaging.Biochemical pharmacology · 2022Review
- Overcoming differential tumor penetration of BRAF inhibitors using computationally guided combination therapy.Science advances · 2022Article
- Single-Cell Image-Based Analysis Reveals Chromatin Changes during the Acquisition of Tamoxifen Drug Resistance.Life (Basel, Switzerland) · 2022Article
- TP53 Null Mutations Identify Lung Cancer Cell Lines with Highest Sensitivity to the Nontaxane Microtubule Inhibitor Eribulin.Molecular pharmacology · 2021Article
- Quantification of Cellular Drug Biodistribution Addresses Challenges in EvaluatingAdvanced therapeutics · 2021Article
- Current Insights and Advancements in Head and Neck Cancer: Emerging Biomarkers and Therapeutics with Cues from Single Cell and 3D Model Omics Profiling.Frontiers in oncology · 2021Review
- Understanding the in vivo Fate of Advanced Materials by Imaging.Advanced functional materials · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Eribulin mesylate was developed as a potent microtubule-targeting cytotoxic agent to treat taxane-resistant cancers, but recent clinical trials have shown that it eventually fails in many patient subpopulations for unclear reasons. To investigate its resistance mechanisms, we developed a fluorescent analog of eribulin with pharmacokinetic (PK) properties and cytotoxic activity across a human cell line panel that are sufficiently similar to the parent drug to study its cellular PK and tissue distribution. Using intravital imaging and automated tracking of cellular dynamics, we found that resistance to eribulin and the fluorescent analog depended directly on the multidrug resistance protein 1 (MDR1). Intravital imaging allowed for real-time analysis of in vivo PK in tumors that were engineered to be spatially heterogeneous for taxane resistance, whereby an MDR1-mApple fusion protein distinguished resistant cells fluorescently. In vivo, MDR1-mediated drug efflux and the three-dimensional tumor vascular architecture were discovered to be critical determinants of drug accumulation in tumor cells. We furthermore show that standard intravenous administration of a third-generation MDR1 inhibitor, HM30181, failed to rescue drug accumulation; however, the same MDR1 inhibitor encapsulated within a nanoparticle delivery system reversed the multidrug-resistant phenotype and potentiated the eribulin effect in vitro and in vivo in mice. Our work demonstrates that in vivo assessment of cellular PK of an anticancer drug is a powerful strategy for elucidating mechanisms of drug resistance in heterogeneous tumors and evaluating strategies to overcome this resistance.
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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.