ArticleProceedings of the National Academy of Sciences of the United States of America2013
Cell motility and drug gradients in the emergence of resistance to chemotherapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. 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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Who cites it
48 citing papers in PubMed, 99 citations in OpenAlex.
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- Deciphering and steering population-level response under spatial drug heterogeneity on microhabitat structures.bioRxiv : the preprint server for biology · 2025Article
- Micro-hydrogel molding-assisted fabrication of a PDMS-based microfluidic concentration-gradient generator for dynamic anticancer drug testing.RSC advances · 2025Article
- Linking spatial drug heterogeneity to microbial growth dynamics in theory and experiment.bioRxiv : the preprint server for biology · 2024Article
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- Diverse mutant selection windows shape spatial heterogeneity in evolving populations.bioRxiv : the preprint server for biology · 2023Article
- Discovery of Proteins Responsible for Resistance to Three Chemotherapy Drugs in Breast Cancer Cells Using Proteomics and Bioinformatics Analysis.Molecules (Basel, Switzerland) · 2022Article
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- The role of chemotaxis and efflux pumps on nitrate reduction in the toxic regions of a ciprofloxacin concentration gradient.The ISME journal · 2021Article
- Breast tumor-on-chip models: From disease modeling to personalized drug screening.Journal of controlled release : official journal of the Controlled Release Society · 2021Review
- Advanced Multi-Dimensional Cellular Models as Emerging Reality to ReproduceInternational journal of molecular sciences · 2021Review
- 3D Scaffolds to Model the Hematopoietic Stem Cell Niche: Applications and Perspectives.Materials (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The emergence of resistance to chemotherapy by cancer cells, when combined with metastasis, is the primary driver of mortality in cancer and has proven to be refractory to many efforts. Theory and computer modeling suggest that the rate of emergence of resistance is driven by the strong selective pressure of mutagenic chemotherapy and enhanced by the motility of mutant cells in a chemotherapy gradient to areas of higher drug concentration and lower population competition. To test these models, we constructed a synthetic microecology which superposed a mutagenic doxorubicin gradient across a population of motile, metastatic breast cancer cells (MDA-MB-231). We observed the emergence of MDA-MB-231 cancer cells capable of proliferation at 200 nM doxorubicin in this complex microecology. Individual cell tracking showed both movement of the MDA-MB-231 cancer cells toward higher drug concentrations and proliferation of the cells at the highest doxorubicin concentrations within 72 h, showing the importance of both motility and drug gradients in the emergence of 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.