ArticleFrontiers in physiology2020
Drug-Induced Resistance in Micrometastases: Analysis of Spatio-Temporal Cell Lineages.
Article in Frontiers in physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 29 citations in OpenAlex.
- Validating the predictions of mathematical models describing tumor growth and treatment response.ArXiv · 2025Article
- Cytoskeletal gene alterations linked to sorafenib resistance in hepatocellular carcinoma.World journal of surgical oncology · 2024Article
- LinG3D: visualizing the spatio-temporal dynamics of clonal evolution.BMC bioinformatics · 2024Article
- The bone ecosystem facilitates multiple myeloma relapse and the evolution of heterogeneous drug resistant disease.Nature communications · 2024Article
- Histology-guided mathematical model of tumor oxygenation: sensitivity analysis of physical and computational parameters.bioRxiv : the preprint server for biology · 2024Article
- Intermetastatic and Intrametastatic Heterogeneity Shapes Adaptive Therapy Cycling Dynamics.Cancer research · 2023Article
- Data-driven spatio-temporal modelling of glioblastoma.Royal Society open science · 2023Review
- Efficient Bayesian inference for stochastic agent-based models.PLoS computational biology · 2022Article
- Drug-induced resistance evolution necessitates less aggressive treatment.PLoS computational biology · 2021Article
- Bridging cell-scale simulations and radiologic images to explain short-time intratumoral oxygen fluctuations.PLoS computational biology · 2021Article
- Collective Cell Migration in a Fibrous Environment: A Hybrid Multiscale Modelling Approach.Frontiers in applied mathematics and statistics · 2021Article
- Single-Cell Techniques and Deep Learning in Predicting Drug Response.Trends in pharmacological sciences · 2020Review
- The CCL5/CCR5 Axis in Cancer Progression.Cancers · 2020Review
- Comparison of Drug Inhibitory Effects (Bulletin of mathematical biology · 2020Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Resistance to anti-cancer drugs is a major cause of treatment failure. While several intracellular mechanisms of resistance have been postulated, the role of extrinsic factors in the development of resistance in individual tumor cells is still not fully understood. Here we used a hybrid agent-based model to investigate how sensitive tumor cells develop drug resistance in the heterogeneous tumor microenvironment. We characterized the spatio-temporal evolution of lineages of the resistant cells and examined how resistance at the single-cell level contributes to the overall tumor resistance. We also developed new methods to track tumor cell adaptation, to trace cell viability trajectories and to examine the three-dimensional spatio-temporal lineage trees. Our findings indicate that drug-induced resistance can result from cells adaptation to the changes in drug distribution. Two modes of cell adaptation were identified that coincide with microenvironmental niches-areas sheltered by cell micro-communities (protectorates) or regions with limited drug penetration (refuga or sanctuaries). We also recognized that certain cells gave rise to lineages of resistant cells (precursors of resistance) and pinpointed three temporal periods and spatial locations at which such cells emerged. This supports the hypothesis that tumor micrometastases do not need to harbor cell populations with pre-existing resistance, but that individual tumor cells can adapt and develop resistance induced by the drug during the treatment.
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