Emma Hammarlund
Research team manager
Poly-aneuploid cancer cells promote evolvability, generating lethal cancer
Author
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