A statistical framework for detecting therapy-induced resistance from drug screens

Abstract Resistance to therapy remains a significant challenge in cancer treatment, often due to the presence of a stem-like cell population that drives tumor recurrence post-treatment. Moreover, many anticancer therapies induce plasticity, converting initially drug-sensitive cells to a more resista...

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Main Authors: Chenyu Wu, Einar Bjarki Gunnarsson, Jasmine Foo, Kevin Leder
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Systems Biology and Applications
Online Access:https://doi.org/10.1038/s41540-025-00560-8
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author Chenyu Wu
Einar Bjarki Gunnarsson
Jasmine Foo
Kevin Leder
author_facet Chenyu Wu
Einar Bjarki Gunnarsson
Jasmine Foo
Kevin Leder
author_sort Chenyu Wu
collection DOAJ
description Abstract Resistance to therapy remains a significant challenge in cancer treatment, often due to the presence of a stem-like cell population that drives tumor recurrence post-treatment. Moreover, many anticancer therapies induce plasticity, converting initially drug-sensitive cells to a more resistant state, e.g. through epigenetic processes and de-differentiation programs. Understanding the balance between therapeutic anti-tumor effects and induced resistance is critical for identifying treatment strategies. In this study, we present a robust statistical framework leveraging multi-type branching process models to characterize the evolutionary dynamics of tumor cell populations. This approach enables the detection and quantification of therapy-induced resistance using high-throughput drug screening data involving total cell counts, without requiring information on subpopulation counts. The framework is validated using both simulated (in silico) and recent experimental (in vitro) datasets, demonstrating its ability to generate meaningful predictions.
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institution Kabale University
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publishDate 2025-08-01
publisher Nature Portfolio
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series npj Systems Biology and Applications
spelling doaj-art-e908b5a1473b4b4f8c2879252ec58fce2025-08-20T03:42:53ZengNature Portfolionpj Systems Biology and Applications2056-71892025-08-0111111910.1038/s41540-025-00560-8A statistical framework for detecting therapy-induced resistance from drug screensChenyu Wu0Einar Bjarki Gunnarsson1Jasmine Foo2Kevin Leder3Department of Industrial and Systems Engineering, University of MinnesotaDivision of Applied Mathematics, Science Institute, University of IcelandSchool of Mathematics, University of MinnesotaDepartment of Industrial and Systems Engineering, University of MinnesotaAbstract Resistance to therapy remains a significant challenge in cancer treatment, often due to the presence of a stem-like cell population that drives tumor recurrence post-treatment. Moreover, many anticancer therapies induce plasticity, converting initially drug-sensitive cells to a more resistant state, e.g. through epigenetic processes and de-differentiation programs. Understanding the balance between therapeutic anti-tumor effects and induced resistance is critical for identifying treatment strategies. In this study, we present a robust statistical framework leveraging multi-type branching process models to characterize the evolutionary dynamics of tumor cell populations. This approach enables the detection and quantification of therapy-induced resistance using high-throughput drug screening data involving total cell counts, without requiring information on subpopulation counts. The framework is validated using both simulated (in silico) and recent experimental (in vitro) datasets, demonstrating its ability to generate meaningful predictions.https://doi.org/10.1038/s41540-025-00560-8
spellingShingle Chenyu Wu
Einar Bjarki Gunnarsson
Jasmine Foo
Kevin Leder
A statistical framework for detecting therapy-induced resistance from drug screens
npj Systems Biology and Applications
title A statistical framework for detecting therapy-induced resistance from drug screens
title_full A statistical framework for detecting therapy-induced resistance from drug screens
title_fullStr A statistical framework for detecting therapy-induced resistance from drug screens
title_full_unstemmed A statistical framework for detecting therapy-induced resistance from drug screens
title_short A statistical framework for detecting therapy-induced resistance from drug screens
title_sort statistical framework for detecting therapy induced resistance from drug screens
url https://doi.org/10.1038/s41540-025-00560-8
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