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LU

Emma Hammarlund

Research team manager

LU

Poly-aneuploid cancer cells promote evolvability, generating lethal cancer

Author

  • Kenneth J. Pienta
  • Emma U. Hammarlund
  • Robert Axelrod
  • Joel S. Brown
  • Sarah R. Amend

Summary, in English

Cancer cells utilize the forces of natural selection to evolve evolvability allowing a constant supply of heritable variation that permits a cancer species to evolutionary track changing hazards and opportunities. Over time, the dynamic tumor ecosystem is exposed to extreme, catastrophic changes in the conditions of the tumor—natural (e.g., loss of blood supply) or imposed (therapeutic). While the nature of these catastrophes may be varied or unique, their common property may be to doom the current cancer phenotype unless it evolves rapidly. Poly-aneuploid cancer cells (PACCs) may serve as efficient sources of heritable variation that allows cancer cells to evolve rapidly, speciate, evolutionarily track their environment, and most critically for patient outcome and survival, permit evolutionary rescue, therapy resistance, and metastasis. As a conditional evolutionary strategy, they permit the cancer cells to accelerate evolution under stress and slow down the generation of heritable variation when conditions are more favorable or when the cancer cells are closer to an evolutionary optimum. We hypothesize that they play a critical and outsized role in lethality by their increased capacity for invasion and motility, for enduring novel and stressful environments, and for generating heritable variation that can be dispensed to their 2N+ aneuploid progeny that make up the bulk of cancer cells within a tumor, providing population rescue in response to therapeutic stress. Targeting PACCs is essential to cancer therapy and patient cure—without the eradication of the resilient PACCs, cancer will recur in treated patients.

Department/s

  • Division of Translational Cancer Research
  • LUCC: Lund University Cancer Centre

Publishing year

2020

Language

English

Pages

1626-1634

Publication/Series

Evolutionary Applications

Volume

13

Issue

7

Document type

Journal article

Publisher

Wiley-Blackwell

Topic

  • Cancer and Oncology

Keywords

  • cancer ecology
  • cancer lethality
  • cancer speciation
  • evolvability
  • metastasis
  • PGCC
  • poly-aneuploid cancer cell
  • polyploid giant cancer cell
  • therapeutic resistance
  • therapy resistance

Status

Published

ISBN/ISSN/Other

  • ISSN: 1752-4563