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Pré-Publication, Document De Travail Année : 2024

The development of drug resistance in metastatic tumours under chemotherapy: an evolutionary perspective

Le développement de la pharmacorésistance dans les tumeurs métastatiques sous chimiothérapie: une perspective évolutive

Federica Padovano
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Chiara Villa
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  • PersonId : 1387557

Résumé

We present a mathematical model of the evolutionary dynamics of a metastatic tumour under chemotherapy, comprising non-local partial differential equations for the phenotype-structured cell populations in the primary tumour and its metastasis. These equations are coupled with a physiologically-based pharmacokinetic model of drug delivery, implementing a realistic delivery schedule. The model is carefully calibrated from the literature, focusing on BRAF-mutated melanoma treated with Dabrafenib as a case study. By means of long-time asymptotic analysis, global sensitivity analysis and numerical simulations, we explore the impact of cell migration from the primary to the metastatic site, physiological aspects of the tumour sites and drug dose on the development of drug resistance and treatment efficacy. Our findings provide a possible explanation for empirical evidence indicating that chemotherapy may foster metastatic spread and that metastatic sites may be less impacted by chemotherapy.
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Dates et versions

hal-04595087 , version 1 (30-05-2024)
hal-04595087 , version 2 (20-06-2024)

Identifiants

  • HAL Id : hal-04595087 , version 1

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Federica Padovano, Luis Almeida, Chiara Villa. The development of drug resistance in metastatic tumours under chemotherapy: an evolutionary perspective. 2024. ⟨hal-04595087v1⟩
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