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LU

Emma Hammarlund

Research team manager

LU

A life history model of the ecological and evolutionary dynamics of polyaneuploid cancer cells

Author

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

Summary, in English

Therapeutic resistance is one of the main reasons for treatment failure in cancer patients. The polyaneuploid cancer cell (PACC) state has been shown to promote resistance by providing a refuge for cancer cells from the effects of therapy and by helping them adapt to a variety of environmental stressors. This state is the result of aneuploid cancer cells undergoing whole genome doubling and skipping mitosis, cytokinesis, or both. In this paper, we create a novel mathematical framework for modeling the eco-evolutionary dynamics of state-structured populations and use this framework to construct a model of cancer populations with an aneuploid and a PACC state. Using in silico simulations, we explore how the PACC state allows cancer cells to (1) survive extreme environmental conditions by exiting the cell cycle after S phase and protecting genomic material and (2) aid in adaptation to environmental stressors by increasing the cancer cell’s ability to generate heritable variation (evolvability) through the increase in genomic content that accompanies polyploidization. In doing so, we demonstrate the ability of the PACC state to allow cancer cells to persist under therapy and evolve therapeutic resistance. By eliminating cells in the PACC state through appropriately-timed PACC-targeted therapies, we show how we can prevent the emergence of resistance and promote cancer eradication.

Department/s

  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
  • EpiHealth: Epidemiology for Health
  • Molecular Evolution
  • LUCC: Lund University Cancer Centre
  • Division of Translational Cancer Research

Publishing year

2022

Language

English

Publication/Series

Scientific Reports

Volume

12

Issue

1

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Cell and Molecular Biology

Status

Published

Research group

  • Molecular Evolution

ISBN/ISSN/Other

  • ISSN: 2045-2322