A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-09-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-42368-8 |
| _version_ | 1827723505817354240 |
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| author | Anuraag Bukkuri Kenneth J. Pienta Robert H. Austin Emma U. Hammarlund Sarah R. Amend Joel S. Brown |
| author_facet | Anuraag Bukkuri Kenneth J. Pienta Robert H. Austin Emma U. Hammarlund Sarah R. Amend Joel S. Brown |
| author_sort | Anuraag Bukkuri |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:00:42Z |
| format | Article |
| id | doaj.art-bcbd6c09da064051a756848a4f23f88c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T22:00:42Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bcbd6c09da064051a756848a4f23f88c2023-11-19T12:58:11ZengNature PortfolioScientific Reports2045-23222023-09-0113111110.1038/s41598-023-42368-8A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populationsAnuraag Bukkuri0Kenneth J. Pienta1Robert H. Austin2Emma U. Hammarlund3Sarah R. Amend4Joel S. Brown5Cancer Biology and Evolution Program and Department of Integrated Mathematical Oncology, Moffitt Cancer CenterThe Brady Urological Institute, Johns Hopkins School of MedicineDepartment of Physics, Princeton UniversityTissue Development and Evolution Research Group, Department of Laboratory Medicine, Lund UniversityThe Brady Urological Institute, Johns Hopkins School of MedicineCancer Biology and Evolution Program and Department of Integrated Mathematical Oncology, Moffitt Cancer CenterAbstract 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.https://doi.org/10.1038/s41598-023-42368-8 |
| spellingShingle | Anuraag Bukkuri Kenneth J. Pienta Robert H. Austin Emma U. Hammarlund Sarah R. Amend Joel S. Brown A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations Scientific Reports |
| title | A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations |
| title_full | A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations |
| title_fullStr | A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations |
| title_full_unstemmed | A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations |
| title_short | A mathematical investigation of polyaneuploid cancer cell memory and cross-resistance in state-structured cancer populations |
| title_sort | mathematical investigation of polyaneuploid cancer cell memory and cross resistance in state structured cancer populations |
| url | https://doi.org/10.1038/s41598-023-42368-8 |
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