ArticleNAR cancer2021
A mechanistic model captures the emergence and implications of non-genetic heterogeneity and reversible drug resistance in ER+ breast cancer cells.
Article in NAR cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 74 citations in OpenAlex.
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Systems-level analysis identifies IRF6 as an inhibitor of epithelial-mesenchymal transition.Journal of biological engineering · 2026Article
- Nrf2 Is Associated with Metastasis-Related Processes in a Chemoresistant Breast Cancer Model: Insights from siRNA Modulation.International journal of molecular sciences · 2026Article
- Endocrine therapy-specific lineage and partial epithelial-mesenchymal reprogramming defines divergent resistant cell-states in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Bidirectional coupling among EMT, AXL-RB1 signaling and lineage switch drives resistance to osimertinib and worse clinical outcomes in NSCLC.bioRxiv : the preprint server for biology · 2026Article
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.BMC cancer · 2026Article
- Decoding breast cancer: insights into molecular pathways & therapeutic approaches.Discover oncology · 2025Review
- Regulatory network and spatial modeling reveal cooperative mechanisms of resistance and immune escape in ER+ breast cancer.bioRxiv : the preprint server for biology · 2025Article
- Personalized cancer treatment strategies incorporating irreversible and reversible drug resistance mechanisms.NPJ systems biology and applications · 2025Article
- Low dimensionality of phenotypic space as an emergent property of coordinated teams in biological regulatory networks.iScience · 2025Article
- EMT-driven plasticity prospectively increases cell-cell variability to promote therapeutic adaptation in breast cancer.Cancer cell international · 2025Article
- Negligible Long-Term Impact of Nonlinear Growth Dynamics on Heterogeneity in Models of Cancer Cell Populations.Bulletin of mathematical biology · 2025Article
- Cancer drug-tolerant persister cells: from biological questions to clinical opportunities.Nature reviews. Cancer · 2024Review
- Tamoxifen metabolites treatment promotes ERα+ transition to triple negative phenotype in vitro, effects of LDL in chemoresistance.Bioscience reports · 2024Article
- Epithelial-mesenchymal plasticity in cancer: signaling pathways and therapeutic targets.MedComm · 2024Review
- Self-consistent signal transduction analysis for modeling context-specific signaling cascades and perturbations.NPJ systems biology and applications · 2024Article
- Increased prevalence of hybrid epithelial/mesenchymal state and enhanced phenotypic heterogeneity in basal breast cancer.iScience · 2024Article
- Article
- Semi-mechanistic modeling of resistance development to β-lactam and β-lactamase-inhibitor combinations.Journal of pharmacokinetics and pharmacodynamics · 2024Article
- Proneural-mesenchymal antagonism dominates the patterns of phenotypic heterogeneity in glioblastoma.iScience · 2024Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to anti-estrogen therapy is an unsolved clinical challenge in successfully treating ER+ breast cancer patients. Recent studies have demonstrated the role of non-genetic (i.e. phenotypic) adaptations in tolerating drug treatments; however, the mechanisms and dynamics of such non-genetic adaptation remain elusive. Here, we investigate coupled dynamics of epithelial-mesenchymal transition (EMT) in breast cancer cells and emergence of reversible drug resistance. Our mechanism-based model for underlying regulatory network reveals that these two axes can drive one another, thus enabling non-genetic heterogeneity in a cell population by allowing for six co-existing phenotypes: epithelial-sensitive, mesenchymal-resistant, hybrid E/M-sensitive, hybrid E/M-resistant, mesenchymal-sensitive and epithelial-resistant, with the first two ones being most dominant. Next, in a population dynamics framework, we exemplify the implications of phenotypic plasticity (both drug-induced and intrinsic stochastic switching) and/or non-genetic heterogeneity in promoting population survival in a mixture of sensitive and resistant cells, even in the absence of any cell-cell cooperation. Finally, we propose the potential therapeutic use of mesenchymal-epithelial transition inducers besides canonical anti-estrogen therapy to limit the emergence of reversible drug resistance. Our results offer mechanistic insights into empirical observations on EMT and drug resistance and illustrate how such dynamical insights can be exploited for better therapeutic designs.
Identifiers
What Socratic holds
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 Socratic graph.