Speaker
Description
Metastatic relapse can occur years after diagnosis, highlighting the need to better understand the mechanisms behind cancer cell dormancy and reactivation.
Here we present a mathematical model, \cite{Sf} that integrates cancer-cell dormancy, reactivation, proliferation and death, tested/calibrated with experimental murine metastasis datasets. The model couples population dynamics with statistical representations of dormancy times, enabling for a systematic comparison of various probability distribution functions.
To this end we study two complementary experimental settings: a) lung metastasis including post-extravasation cancer cell death, \cite{Ca} and b) liver metastasis without cell death, \cite{Na}. When cancer cell death is present, heavy-tailed dormancy distributions better fit to the experimental tumour progression data, and predict prolonged dormancy periods consistent with delayed metastatic relapse. In contrast, when cell death is absent, heavy- and light-tailed distributions perform comparably, indicating that heavy-tails emerge as a compensatory mechanism in the presence of cell attrition. These results demonstrate the significance of selecting biologically relevant metastatic progression models.
We conclude that the proposed mathematical model is able to provide a qualitative and quantitative basis for investigating dormancy-driven metastasis and offers a new direction into integrating experimental data with mathematical models for metastasis insights.
Bibliography
@article {Sf,
author = {Sfakianakis, Nikolaos and Katsaounis, Dimitrios and Chaplain, Mark A.J.},
title = {Modelling cancer cell dormancy in mice: statistical distributions predict reactivation times and survival dynamics},
elocation-id = {2025.03.21.644537},
year = {2025},
doi = {10.1101/2025.03.21.644537},
publisher = {Cold Spring Harbor Laboratory},
URL = {https://www.biorxiv.org/content/early/2025/03/25/2025.03.21.644537},
eprint = {https://www.biorxiv.org/content/early/2025/03/25/2025.03.21.644537.full.pdf},
journal = {bioRxiv}
}
@article{Ca,
title={Temporal progression of metastasis in lung: cell survival, dormancy, and location dependence of metastatic inefficiency.},
author={Cameron, M. and Schmidt, E.E. and Kerkvliet, N.A. and Nadkarni, K.V. and Morris, V.L. and Groom, A.C. and Chambers, A.F. and Macdonald, I.C.},
journal={Cancer research},
year={2000},
volume={60 9},
pages={2541-6}
}
@article{Na,
title = {Cellular expression of green fluorescent protein, coupled with high-resolution in vivo videomicroscopy, to monitor steps in tumor metastasis},
volume = {112},
number = {12},
journal = {Journal of Cell Science},
publisher = {The Company of Biologists},
author = {Naumov, G.~N. and Wilson, S.~M. and MacDonald, I.~C. and Schmidt, E.~E. and Morris, V.~L. and Groom, A.~C. and Hoffman, R.~M. and Chambers, A.~F.},
year = {1999},
pages = {1835–1842}
}
