气候变化领域集成服务门户(CCPortal): Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells

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DOI	10.1073/pnas.2020838118
	Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells
	Pienta K.J.; Hammarlund E.U.; Brown J.S.; Amend S.R.; Axelrod R.M.
发表日期	2021
ISSN	00278424
卷号	118 期号:7
英文摘要	We present a unifying theory to explain cancer recurrence, therapeutic resistance, and lethality. The basis of this theory is the formation of simultaneously polyploid and aneuploid cancer cells, polyaneuploid cancer cells (PACCs), that avoid the toxic effects of systemic therapy by entering a state of cell cycle arrest. The theory is independent of which of the classically associated oncogenic mutations have already occurred. PACCs have been generally disregarded as senescent or dying cells. Our theory states that therapeutic resistance is driven by PACC formation that is enabled by accessing a polyploid program that allows an aneuploid cancer cell to double its genomic content, followed by entry into a nondividing cell state to protect DNA integrity and ensure cell survival. Upon removal of stress, e.g., chemotherapy, PACCs undergo depolyploidization and generate resistant progeny that make up the bulk of cancer cells within a tumor. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Metastasis\|drug resistance\|tumor microenvironment\|whole-genome doubling\|evolution
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180672
作者单位	Brady Urological Institute, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States; Translational Cancer Research, Department of Laboratory Medicine, Lund University, Lund, 223 81, Sweden; Nordic Center for Earth Evolution, University of Southern Denmark, Odense, 5230, Denmark; Cancer Biology and Evolution Program, Moffitt Cancer Center, Tampa, FL 33612, United States; Department of Integrated Mathematical Oncology, Moffitt Cancer Center, Tampa, FL 33612, United States; Gerald R. Ford School of Public Policy, University of Michigan, Ann Arbor, MI 48109, United States
推荐引用方式 GB/T 7714	Pienta K.J.,Hammarlund E.U.,Brown J.S.,et al. Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells[J],2021,118(7).
APA	Pienta K.J.,Hammarlund E.U.,Brown J.S.,Amend S.R.,&Axelrod R.M..(2021).Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells.Proceedings of the National Academy of Sciences of the United States of America,118(7).
MLA	Pienta K.J.,et al."Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells".Proceedings of the National Academy of Sciences of the United States of America 118.7(2021).