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Paradoxes of cancer: survival at the brink

Paradoxes of cancer: survival at the brink
Paradoxes of cancer: survival at the brink
The fundamental understanding of how Cancer initiates, persists and then progresses is evolving. High-resolution technologies, including single-cell mutation and gene expression measurements, are now attainable, providing an ever-increasing insight into the molecular details. However, this higher resolution has shown that somatic mutation theory itself cannot explain the extraordinary resistance of cancer to extinction. There is a need for a more Systems-based framework of understanding cancer complexity, which in particular explains the regulation of gene expression during cell-fate decisions. Cancer displays a series of paradoxes. Here we attempt to approach them from the view-point of adaptive exploration of gene regulatory networks at the edge of order and chaos, where cell-fate is changed by oscillations between alternative regulators of cellular senescence and reprogramming operating through self-organisation. On this background, the role of polyploidy in accessing the phylogenetically pre-programmed “oncofetal attractor” state, related to unicellularity, and the de-selection of unsuitable variants at the brink of cell survival is highlighted. The concepts of the embryological and atavistic theory of cancer, cancer cell “life-cycle”, and cancer aneuploidy paradox are dissected under this lense. Finally, we challenge researchers to consider that cancer “defects” are mostly the adaptation tools of survival programs that have arisen during evolution and are intrinsic of cancer. Recognition of these features should help in the development of more successful anti-cancer treatments.
Erenpreisaa, Jekaterina
58e1f4fc-2cf3-45e3-aa18-8ad8b7d9d77a
Salminaa, Kristine
3983a730-d582-40f5-97fa-c185792b1bf5
Anatskaya, Olga
9df05f5f-7df6-4443-8975-1a129f5856f6
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Erenpreisaa, Jekaterina
58e1f4fc-2cf3-45e3-aa18-8ad8b7d9d77a
Salminaa, Kristine
3983a730-d582-40f5-97fa-c185792b1bf5
Anatskaya, Olga
9df05f5f-7df6-4443-8975-1a129f5856f6
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c

Erenpreisaa, Jekaterina, Salminaa, Kristine, Anatskaya, Olga and Cragg, Mark (2020) Paradoxes of cancer: survival at the brink. Seminars in Cancer Biology. (doi:10.1016/j.semcancer.2020.12.009).

Record type: Article

Abstract

The fundamental understanding of how Cancer initiates, persists and then progresses is evolving. High-resolution technologies, including single-cell mutation and gene expression measurements, are now attainable, providing an ever-increasing insight into the molecular details. However, this higher resolution has shown that somatic mutation theory itself cannot explain the extraordinary resistance of cancer to extinction. There is a need for a more Systems-based framework of understanding cancer complexity, which in particular explains the regulation of gene expression during cell-fate decisions. Cancer displays a series of paradoxes. Here we attempt to approach them from the view-point of adaptive exploration of gene regulatory networks at the edge of order and chaos, where cell-fate is changed by oscillations between alternative regulators of cellular senescence and reprogramming operating through self-organisation. On this background, the role of polyploidy in accessing the phylogenetically pre-programmed “oncofetal attractor” state, related to unicellularity, and the de-selection of unsuitable variants at the brink of cell survival is highlighted. The concepts of the embryological and atavistic theory of cancer, cancer cell “life-cycle”, and cancer aneuploidy paradox are dissected under this lense. Finally, we challenge researchers to consider that cancer “defects” are mostly the adaptation tools of survival programs that have arisen during evolution and are intrinsic of cancer. Recognition of these features should help in the development of more successful anti-cancer treatments.

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More information

Accepted/In Press date: 9 December 2020
e-pub ahead of print date: 16 December 2020

Identifiers

Local EPrints ID: 446817
URI: http://eprints.soton.ac.uk/id/eprint/446817
PURE UUID: e0d99e12-6015-440c-9ca2-7ac6d2973be4
ORCID for Mark Cragg: ORCID iD orcid.org/0000-0003-2077-089X

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Date deposited: 23 Feb 2021 17:32
Last modified: 22 Nov 2021 02:42

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Contributors

Author: Jekaterina Erenpreisaa
Author: Kristine Salminaa
Author: Olga Anatskaya
Author: Mark Cragg ORCID iD

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