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Poly-aneuploid cancer cells promote evolvability, generating lethal cancer

Pienta, Kenneth J. ; Hammarlund, Emma U. LU ; Axelrod, Robert ; Brown, Joel S. and Amend, Sarah R. (2020) In Evolutionary Applications 13(7). p.1626-1634
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... (More)

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.

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; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cancer ecology, cancer lethality, cancer speciation, evolvability, metastasis, PGCC, poly-aneuploid cancer cell, polyploid giant cancer cell, therapeutic resistance, therapy resistance
in
Evolutionary Applications
volume
13
issue
7
pages
9 pages
publisher
Wiley-Blackwell
external identifiers
  • scopus:85086323145
ISSN
1752-4563
DOI
10.1111/eva.12929
language
English
LU publication?
yes
id
998a707f-8632-4770-ad6d-5a4c461ae535
date added to LUP
2020-12-22 10:50:05
date last changed
2020-12-29 04:18:51
@article{998a707f-8632-4770-ad6d-5a4c461ae535,
  abstract     = {<p>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.</p>},
  author       = {Pienta, Kenneth J. and Hammarlund, Emma U. and Axelrod, Robert and Brown, Joel S. and Amend, Sarah R.},
  issn         = {1752-4563},
  language     = {eng},
  number       = {7},
  pages        = {1626--1634},
  publisher    = {Wiley-Blackwell},
  series       = {Evolutionary Applications},
  title        = {Poly-aneuploid cancer cells promote evolvability, generating lethal cancer},
  url          = {http://dx.doi.org/10.1111/eva.12929},
  doi          = {10.1111/eva.12929},
  volume       = {13},
  year         = {2020},
}