TY - JOUR
T1 - The life cycle of polyploid giant cancer cells and dormancy in cancer
T2 - Opportunities for novel therapeutic interventions
AU - Liu, Jinsong
AU - Niu, Na
AU - Li, Xiaoran
AU - Zhang, Xudong
AU - Sood, Anil K.
N1 - Funding Information:
The authors thank Ms. Kim Vu for graphic rendering. This work was supported, in part, by the Moonshot program in Ovarian Cancer at The University of Texas MD Anderson Cancer CenterSPORE in Ovarian Cancer (CA217685), and the American Cancer Society. We thank Erica Goodoff, Senior Scientific Editor in the Research Medical Library at The University of Texas MD Anderson Cancer Center, for editing this article, and two reviewers for their constructive comments to improve this manuscript. This paper is the fourth in a series of papers on the enigma of the origin of human tumors.
Funding Information:
The authors thank Ms. Kim Vu for graphic rendering. This work was supported, in part, by the Moonshot program in Ovarian Cancer at The University of Texas MD Anderson Cancer Center SPORE in Ovarian Cancer ( CA217685 ), and the American Cancer Society . We thank Erica Goodoff, Senior Scientific Editor in the Research Medical Library at The University of Texas MD Anderson Cancer Center, for editing this article, and two reviewers for their constructive comments to improve this manuscript.
Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2022/6
Y1 - 2022/6
N2 - Recent data suggest that most genotoxic agents in cancer therapy can lead to shock of genome and increase in cell size, which leads whole genome duplication or multiplication, formation of polyploid giant cancer cells, activation of an early embryonic program, and dedifferentiation of somatic cells. This process is achieved via the giant cell life cycle, a recently proposed mechanism for malignant transformation of somatic cells. Increase in both cell size and ploidy allows cells to completely or partially restructures the genome and develop into a blastocyst-like structure, similar to that observed in blastomere-stage embryogenesis. Although blastocyst-like structures with reprogrammed genome can generate resistant or metastatic daughter cells or benign cells of different lineages, they also acquired ability to undergo embryonic diapause, a reversible state of suspended embryonic development in which cells enter dormancy for survival in response to environmental stress. Therapeutic agents can activate this evolutionarily conserved developmental program, and when cells awaken from embryonic diapause, this leads to recurrence or metastasis. Understanding of the key mechanisms that regulate the different stages of the giant cell life cycle offers new opportunities for therapeutic intervention.
AB - Recent data suggest that most genotoxic agents in cancer therapy can lead to shock of genome and increase in cell size, which leads whole genome duplication or multiplication, formation of polyploid giant cancer cells, activation of an early embryonic program, and dedifferentiation of somatic cells. This process is achieved via the giant cell life cycle, a recently proposed mechanism for malignant transformation of somatic cells. Increase in both cell size and ploidy allows cells to completely or partially restructures the genome and develop into a blastocyst-like structure, similar to that observed in blastomere-stage embryogenesis. Although blastocyst-like structures with reprogrammed genome can generate resistant or metastatic daughter cells or benign cells of different lineages, they also acquired ability to undergo embryonic diapause, a reversible state of suspended embryonic development in which cells enter dormancy for survival in response to environmental stress. Therapeutic agents can activate this evolutionarily conserved developmental program, and when cells awaken from embryonic diapause, this leads to recurrence or metastasis. Understanding of the key mechanisms that regulate the different stages of the giant cell life cycle offers new opportunities for therapeutic intervention.
KW - Dormancy
KW - Embryonic diapause
KW - Giant cell life cycle (giant cell cycle)
KW - Polyploid giant cancer cells
KW - Therapeutic resistance
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U2 - 10.1016/j.semcancer.2021.10.005
DO - 10.1016/j.semcancer.2021.10.005
M3 - Review article
C2 - 34670140
AN - SCOPUS:85117723538
SN - 1044-579X
VL - 81
SP - 132
EP - 144
JO - Seminars in cancer biology
JF - Seminars in cancer biology
ER -