ArticleIntegrative biology : quantitative biosciences from nano to macro2017
A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance.
Article in Integrative biology : quantitative biosciences from nano to macro, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 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
29 citing papers in PubMed, 49 citations in OpenAlex.
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- Matrix Stiffness and Biochemistry Govern Colorectal Cancer Cell Growth and Signaling in User-Programmable Synthetic Hydrogels.ACS biomaterials science & engineering · 2025Article
- Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.Journal of hematology & oncology · 2025Review
- Human breast tissue engineering in health and disease.EMBO molecular medicine · 2024Review
- Article
- Extracellular Matrix Cues Regulate Mechanosensing and Mechanotransduction of Cancer Cells.Cells · 2024Review
- Phosphoproteomic Changes Induced by Cell-Derived Matrix and Their Effect on Tumor Cell Migration and Cytoskeleton Remodeling.ACS biomaterials science & engineering · 2023Article
- Synthetic living materials in cancer biology.Nature reviews bioengineering · 2023Article
- Towards a standardized multi-tissue decellularization protocol for the derivation of extracellular matrix materials.Biomaterials science · 2023Article
- GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids.Pharmaceutics · 2023Article
- Extracellular matrix stiffness activates mechanosensitive signals but limits breast cancer cell spheroid proliferation and invasion.Frontiers in cell and developmental biology · 2023Article
- The role of ADAM8 in the mechanophenotype of MDA-MB-231 breast cancer cells in 3D extracellular matrices.Frontiers in cell and developmental biology · 2023Article
- Challenges and Opportunities Modeling the Dynamic Tumor Matrisome.BME frontiers · 2023Review
- The role of matrix stiffness in breast cancer progression: a review.Frontiers in oncology · 2023Review
- Biological role of matrix stiffness in tumor growth and treatment.Journal of translational medicine · 2022Review
- A lineage tree-based hidden Markov model quantifies cellular heterogeneity and plasticity.Communications biology · 2022Article
- Systems approaches to uncovering the contribution of environment-mediated drug resistance.Current opinion in solid state & materials science · 2022Article
- The extracellular matrix alteration, implication in modulation of drug resistance mechanism: friends or foes?Journal of experimental & clinical cancer research : CR · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments.
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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.