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

Anuraag Bukkuri, Kenneth J. Pienta, Robert H. Austin, Emma U. Hammarlund, Sarah R. Amend, Joel S. Brown

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Article number15027
JournalScientific reports
Volume13
Issue number1
DOIs
StatePublished - Dec 2023

All Science Journal Classification (ASJC) codes

  • General

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