Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer

Clinical experience demonstrates that prostate cancer has a remarkable capacity to evolve resistance to all currently available treatments resulting in progression and, ultimately, patient death. Resistance mechanisms often come at a fitness cost placing cells in a bind when competing with surrounding cells. A carefully chosen secondary drug can introduce a double-bind targeting the adaptive resistance mechanism. This manuscript provides the first direct experimental evidence quantifying an "evolutionary double-bind' in prostate cancer supporting the combination of DNA-damaging agents and NK cell-based immunotherapy in evolutionarily guided treatment designs. Our work is mathematically novel in that it extends Evolutionary Game Theory models and establishes an experimental-mathematical framework to quantify genuine evolutionary double binds applicable across cancer types and treatment modalities.

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Institutions

Publication Details

Journal
International Journal of Radiation Oncology*Biology*Physics
Published
2025-09-23
DOI
https://doi.org/10.1016/j.ijrobp.2025.09.034
Citations
3
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
2.39

Funders

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article

Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer

Hannah Newman, Laure Marignol, Bina Desai, Jacintha O’Sullivan et al.
3 citations
International Journal of Radiation Oncology*Biology*Physics
Immune Cell Function and Interaction
2.39
article

Evolutionary Double-Bind Treatment Using Radiation Therapy and Natural Killer Cell-Based Immunotherapy in Prostate Cancer

Hannah Newman, Laure Marignol, Bina Desai, Jacintha O’Sullivan, A. Ojeda, Robert A. Gatenby, Taylor M. Bursell, Jeffrey West, Sarah Barrett, Alexander R.A. Anderson, Mark Robertson‐Tessi, Kimberly A. Luddy, Verónica Estrella, Cliona O’Farrelly, Joel S. Brown
article en
3 citations

Abstract

Clinical experience demonstrates that prostate cancer has a remarkable capacity to evolve resistance to all currently available treatments resulting in progression and, ultimately, patient death. Resistance mechanisms often come at a fitness cost placing cells in a bind when competing with surrounding cells. A carefully chosen secondary drug can introduce a double-bind targeting the adaptive resistance mechanism. This manuscript provides the first direct experimental evidence quantifying an "evolutionary double-bind' in prostate cancer supporting the combination of DNA-damaging agents and NK cell-based immunotherapy in evolutionarily guided treatment designs. Our work is mathematically novel in that it extends Evolutionary Game Theory models and establishes an experimental-mathematical framework to quantify genuine evolutionary double binds applicable across cancer types and treatment modalities.

International Journal of Radiation Oncology*Biology*PhysicsVol. 124(3)
Trinity College (CA), Trinity College Dublin (IE), Moffitt Cancer Center (US)
Science Foundation Ireland, National Cancer Institute
Openalex Percentile: Top 10%
Immune Cell Function and Interaction
2.39
DOIOpen Access PDFOpenAlex
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