Poly-aneuploid cancer cells promote evolvability, generating lethal cancer

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
Organisations
External organisations
  • Johns Hopkins University School of Medicine
  • University of Southern Denmark
  • University of Michigan
  • H. Lee Moffitt Cancer Center & Research Institute
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • 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
Original languageEnglish
Pages (from-to)1626-1634
Number of pages9
JournalEvolutionary Applications
Volume13
Issue number7
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes