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A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations

Bukkuri, Anuraag LU ; Pienta, Kenneth J. LU ; Austin, Robert H. ; Hammarlund, Emma U. LU ; Amend, Sarah R. and Brown, Joel S. (2023) In Scientific Reports 13(1).
Abstract

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)

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.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
13
issue
1
article number
15027
publisher
Nature Publishing Group
external identifiers
  • scopus:85170675624
  • pmid:37700000
ISSN
2045-2322
DOI
10.1038/s41598-023-42368-8
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2023, Springer Nature Limited.
id
001e090b-9f5c-4100-82eb-73fbcb1a403c
date added to LUP
2023-12-04 15:33:50
date last changed
2025-10-17 15:51:24
@article{001e090b-9f5c-4100-82eb-73fbcb1a403c,
  abstract     = {{<p>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.</p>}},
  author       = {{Bukkuri, Anuraag and Pienta, Kenneth J. and Austin, Robert H. and Hammarlund, Emma U. and Amend, Sarah R. and Brown, Joel S.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations}},
  url          = {{http://dx.doi.org/10.1038/s41598-023-42368-8}},
  doi          = {{10.1038/s41598-023-42368-8}},
  volume       = {{13}},
  year         = {{2023}},
}