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Main Authors: Yue, Rui, Li, Chenghang, Lei, Jinzhi
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2605.17208
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author Yue, Rui
Li, Chenghang
Lei, Jinzhi
author_facet Yue, Rui
Li, Chenghang
Lei, Jinzhi
contents Adaptive therapy (AT) is designed to postpone the emergence of drug resistance by exploiting evolutionary competition among tumor subclones. Most mathematical models of AT assume a binary population structure of drug-sensitive and drug-resistant cells, which neglects the continuous nature of phenotypic plasticity. In this study, we propose a mathematical model that integrates a continuous drug susceptibility index with a probabilistic inheritance function to describe clonal dynamics under therapy. The resulting integro-differential system generalizes traditional two-type competition models and captures both heterogeneity and plasticity of tumor cells. Analytical and numerical studies show that (i) continuous therapy drives rapid expansion of resistant clones, (ii) adaptive therapy maintains long-term tumor control by dynamically regulating sensitive populations, and (iii) high phenotypic plasticity accelerates phenotype switching, leading to earlier tumor relapse following continuous therapy. These results identify critical parameter regimes where adaptive therapy outperforms fixed regimens and highlight the essential role of plasticity in shaping treatment outcomes. The proposed framework provides a more realistic mathematical foundation for the design of clinically relevant adaptive therapy strategies.
format Preprint
id arxiv_https___arxiv_org_abs_2605_17208
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle Modeling tumor cell heterogeneity and plasticity in adaptive therapy
Yue, Rui
Li, Chenghang
Lei, Jinzhi
Populations and Evolution
92C50, 34K99
Adaptive therapy (AT) is designed to postpone the emergence of drug resistance by exploiting evolutionary competition among tumor subclones. Most mathematical models of AT assume a binary population structure of drug-sensitive and drug-resistant cells, which neglects the continuous nature of phenotypic plasticity. In this study, we propose a mathematical model that integrates a continuous drug susceptibility index with a probabilistic inheritance function to describe clonal dynamics under therapy. The resulting integro-differential system generalizes traditional two-type competition models and captures both heterogeneity and plasticity of tumor cells. Analytical and numerical studies show that (i) continuous therapy drives rapid expansion of resistant clones, (ii) adaptive therapy maintains long-term tumor control by dynamically regulating sensitive populations, and (iii) high phenotypic plasticity accelerates phenotype switching, leading to earlier tumor relapse following continuous therapy. These results identify critical parameter regimes where adaptive therapy outperforms fixed regimens and highlight the essential role of plasticity in shaping treatment outcomes. The proposed framework provides a more realistic mathematical foundation for the design of clinically relevant adaptive therapy strategies.
title Modeling tumor cell heterogeneity and plasticity in adaptive therapy
topic Populations and Evolution
92C50, 34K99
url https://arxiv.org/abs/2605.17208