Review
Version 2
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Understanding Cancer from an Evolutionary Perspective; DSCD Cells as Cell-of-Origin in Non-Mutational Sporadic Cancers
Version 1
: Received: 22 August 2023 / Approved: 23 August 2023 / Online: 24 August 2023 (09:43:20 CEST)
Version 2 : Received: 24 December 2023 / Approved: 25 December 2023 / Online: 26 December 2023 (09:54:12 CET)
Version 2 : Received: 24 December 2023 / Approved: 25 December 2023 / Online: 26 December 2023 (09:54:12 CET)
A peer-reviewed article of this Preprint also exists.
Niculescu, V. F. (2024). Understanding cancer from an evolutionary perspective: high-risk reprogramming of genome-damaged stem cells. Academia Medicine, 1. Niculescu, V. F. (2024). Understanding cancer from an evolutionary perspective: high-risk reprogramming of genome-damaged stem cells. Academia Medicine, 1.
Abstract
Background: One of the most astounding discoveries of recent times is the recognition that cancer embodies a transition from a higher level of metazoan cell organization to a more foundational pre-metazoic state. This shift is steered by genes housed within the ancestral genome compartment, pervasive across all metazoan genomes, encompassing humans, and governed by a pre-metazoic gene regulatory mechanism (aGRN). This work aims to highlight the emerging field of evolutionary cancer cell biology (ECCB), which points to the deep homology between cancer and protist life cycles tracing back to the common ancestor of amoebozoans, metazoans, and fungi (AMF). The ECCB analysis reveals the essence of the non-gametogenic germline of the AMF ancestor, which serves as a blueprint for all metazoan germlines and stem cell lineages and controls the life cycle of cancer. Every germ and stem cell lineage of humans and metazoans traces its lineage back to this Urgermline, transmitting crucial processes such as asymmetric cell cycling, differentiation, stemness, and phenomena like GST and SGT (aka EMT and MET) to their subsequent evolutionary descendants. Oxygen-sensitive germline and stem cells suffer DNA-DSB due to stress and oxygen ranges reminiscent of ancestral hyperoxia, leading to cell senescence. Cells that can overcome senescence can proliferate as DSCD cells with defective symmetric cell division, paving the way for malignancy and PGCC cancers. Conclusions: Understanding cancer from its evolutionary origins may help break some of the logjams in cancer prevention and open up new therapeutic pathways.
Keywords
cancer; senescence; asymmetric and symmetric division; loss of function; DNA-damage repair; reprogramming; malignancy
Subject
Medicine and Pharmacology, Oncology and Oncogenics
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Commenter: Vladimir Niculescu
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