ArticlePLoS biology2019
Cancer cell population growth kinetics at low densities deviate from the exponential growth model and suggest an Allee effect.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- The logarithmic phase as a therapeutic direction: evaluating pharmacological strategies against cancer progression.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Characterizing Tumor Cell Movement in Partial Differential Equation Models of Triple-Negative Breast Cancer Receiving Neoadjuvant Therapy.Annals of biomedical engineering · 2026Article
- Simulation Framework to Investigate Efficacy and Ocular Safety of Belantamab Mafodotin Combinations in Relapsed/Refractory Multiple Myeloma.CPT: pharmacometrics & systems pharmacology · 2026Article
- LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro.Molecular oncology · 2026Article
- Deep learning identifies heterogeneous subpopulations in breast cancer cell lines.npj biomedical innovations · 2025Article
- Deformations of acid-mediated invasive tumors in a model with Allee effect.Journal of mathematical biology · 2025Article
- Systems Biology of the Cancer Cell.Annual review of biomedical engineering · 2025Review
- A Mathematical Perspective on the Influence of Allee Effects in Oncolytic Virotherapy.Mathematics (Basel, Switzerland) · 2025Article
- Validating the predictions of mathematical models describing tumor growth and treatment response.ArXiv · 2025Article
- Mapping cell-cell fusion at single-cell resolution.bioRxiv : the preprint server for biology · 2025Article
- Negligible Long-Term Impact of Nonlinear Growth Dynamics on Heterogeneity in Models of Cancer Cell Populations.Bulletin of mathematical biology · 2025Article
- Harnessing the extinction vortex against acute lymphoblastic leukemia.Evolution, medicine, and public health · 2025Article
- The impact of cell density variations on nanoparticle uptake across bioprinted A549 gradients.Frontiers in bioengineering and biotechnology · 2025Article
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- Advancing cancer drug development with mechanistic mathematical modeling: bridging the gap between theory and practice.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Stochastic models allow improved inference of microbiome interactions from time series data.PLoS biology · 2024Article
- Spatial interactions modulate tumor growth and immune infiltration.NPJ systems biology and applications · 2024Article
- Understanding patient-derived tumor organoid growth through an integrated imaging and mathematical modeling framework.PLoS computational biology · 2024Article
- Ultrasensitive Response Explains the Benefit of Combination Chemotherapy Despite Drug Antagonism.Molecular cancer therapeutics · 2024Article
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7 authors.
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Abstract
Most models of cancer cell population expansion assume exponential growth kinetics at low cell densities, with deviations to account for observed slowing of growth rate only at higher densities due to limited resources such as space and nutrients. However, recent preclinical and clinical observations of tumor initiation or recurrence indicate the presence of tumor growth kinetics in which growth rates scale positively with cell numbers. These observations are analogous to the cooperative behavior of species in an ecosystem described by the ecological principle of the Allee effect. In preclinical and clinical models, however, tumor growth data are limited by the lower limit of detection (i.e., a measurable lesion) and confounding variables, such as tumor microenvironment, and immune responses may cause and mask deviations from exponential growth models. In this work, we present alternative growth models to investigate the presence of an Allee effect in cancer cells seeded at low cell densities in a controlled in vitro setting. We propose a stochastic modeling framework to disentangle expected deviations due to small population size stochastic effects from cooperative growth and use the moment approach for stochastic parameter estimation to calibrate the observed growth trajectories. We validate the framework on simulated data and apply this approach to longitudinal cell proliferation data of BT-474 luminal B breast cancer cells. We find that cell population growth kinetics are best described by a model structure that considers the Allee effect, in that the birth rate of tumor cells increases with cell number in the regime of small population size. This indicates a potentially critical role of cooperative behavior among tumor cells at low cell densities with relevance to early stage growth patterns of emerging and relapsed tumors.
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