Document Type
Article
Publication Date
10-14-2025
Identifier
DOI: 10.1007/s11538-025-01508-z; PMCID: PMC12521341
Abstract
Cell heterogeneity plays an important role in patient responses to drug treatments. In many cancers, it is associated with poor treatment outcomes. Many modern drug combination therapies aim to exploit cell heterogeneity, but determining how to optimise responses from heterogeneous cell populations while accounting for multi-drug synergies remains a challenge. In this work, we introduce and analyse a general optimal control framework that can be used to model the treatment response of multiple cell populations that are treated with multiple drugs that mutually interact. In this framework, we model the effect of multiple drugs on the cell populations using a system of coupled semi-linear ordinary differential equations and derive general results for the optimal solutions. We then apply this framework to three canonical examples and discuss the wider question of how to relate mathematical optimality to clinically observable outcomes, introducing a systematic approach to propose qualitatively different classes of drug dosing inspired by optimal control.
Journal Title
Bulletin of mathematical biology
Volume
87
Issue
11
First Page
159
Last Page
159
MeSH Keywords
Humans; Mathematical Concepts; Models, Biological; Neoplasms; Drug Synergism; Antineoplastic Combined Chemotherapy Protocols; Computer Simulation
PubMed ID
41085839
Keywords
Mathematical Concepts; Models, Biological; Neoplasms; Drug Synergism; Antineoplastic Combined Chemotherapy Protocols; Computer Simulation
Recommended Citation
Martina-Perez SF, Johnson SWS, Crossley RM, Kasemeier JC, Kulesa PM, Baker RE. Optimal Control in Combination Therapy for Heterogeneous Cell Populations with Drug Synergies. Bull Math Biol. 2025;87(11):159. Published 2025 Oct 14. doi:10.1007/s11538-025-01508-z
Comments
Grants and funding
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Publisher's Link: https://link.springer.com/article/10.1007/s11538-025-01508-z