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A mathematical inve...
A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations
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- Bukkuri, Anuraag (författare)
- H. Lee Moffitt Cancer Center & Research Institute
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- Pienta, Kenneth J. (författare)
- Johns Hopkins University School of Medicine
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- Austin, Robert H. (författare)
- Princeton University
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- Hammarlund, Emma U. (författare)
- Lund University,Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Molekylär evolution,Forskargrupper vid Lunds universitet,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Molecular Evolution,Lund University Research Groups
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- Amend, Sarah R. (författare)
- Johns Hopkins University School of Medicine
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- Brown, Joel S. (författare)
- H. Lee Moffitt Cancer Center & Research Institute
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H Lee Moffitt Cancer Center & Research Institute Johns Hopkins University School of Medicine (creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The polyaneuploid cancer cell (PACC) state promotes cancer lethality by contributing to survival in extreme conditions and metastasis. Recent experimental evidence suggests that post-therapy PACC-derived recurrent populations display cross-resistance to classes of therapies with independent mechanisms of action. We hypothesize that this can occur through PACC memory, whereby cancer cells that have undergone a polyaneuploid transition (PAT) reenter the PACC state more quickly or have higher levels of innate resistance. In this paper, we build on our prior mathematical models of the eco-evolutionary dynamics of cells in the 2N+ and PACC states to investigate these two hypotheses. We show that although an increase in innate resistance is more effective at promoting cross-resistance, this trend can also be produced via PACC memory. We also find that resensitization of cells that acquire increased innate resistance through the PAT have a considerable impact on eco-evolutionary dynamics and extinction probabilities. This study, though theoretical in nature, can help inspire future experimentation to tease apart hypotheses surrounding how cross-resistance in structured cancer populations arises.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
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