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

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.

Pienta, Kenneth J.Johns Hopkins University School of Medicine(Swepub:lu)ke0368pi (författare)
Austin, Robert H.Princeton University (författare)
Hammarlund, Emma U.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(Swepub:lu)med-ehd (författare)
Amend, Sarah R.Johns Hopkins University School of Medicine (författare)
Brown, Joel S.H. Lee Moffitt Cancer Center & Research Institute (författare)
H. Lee Moffitt Cancer Center & Research InstituteJohns Hopkins University School of Medicine (creator_code:org_t)

Av författaren/redakt...: Bukkuri, Anuraag; Pienta, Kenneth ...; Austin, Robert H ...; Hammarlund, Emma ...; Amend, Sarah R.; Brown, Joel S.

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinska och f ...; och Cell och molekyl ...

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