ArticleProceedings of the National Academy of Sciences of the United States of America2021
Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 106 citations in OpenAlex.
- The Sleeping Giant: Metabolism and Autophagy in the Generation and Survival of Dormant Polyploid Giant Cancer Cells.MedComm · 2026Review
- Hyperwrinkling of the nuclear lamina is associated with attenuated mechanosensitivity in giant nucleated cancer cells.Science advances · 2026Article
- Polyploidy: A macromutational force pushing bioeconomic developments.Proceedings of the National Academy of Sciences of the United States of America · 2026Review
- Clinical Implications of Polyploid Giant Cancer Cells in Solid Tumors: Biology, Diagnosis, and Therapeutic Considerations.Cancers · 2026Review
- Article
- Disrupting Lipid Raft Microdomains to Block Polyploid Giant Cancer Cell Budding and Enhance Radiotherapy Response.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.Scientific reports · 2026Article
- Life history enlightened therapies: cell cycle mapping to identify molecular targets to prevent hepatocellular carcinoma.Evolution, medicine, and public health · 2026Article
- Unscheduled polyploidy synergizes with oncogenic mutations to enhance genome instability and tumorigenesis.Cancer letters · 2025Article
- Cancer cells surviving cisplatin chemotherapy increase stress-induced OMA1 activity and mitochondrial fragmentation.bioRxiv : the preprint server for biology · 2025Article
- Exploiting dysregulated iron homeostasis to eradicate persistent high-grade serous ovarian cancer.Cell death discovery · 2025Article
- Potential role of thymoquinone to treat gastrointestinal cancers: insights into its molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Oncogenic signaling in the Drosophila prostate-like accessory gland activates a pro-tumorigenic program in the absence of proliferation.Disease models & mechanisms · 2025Article
- Temporal myc dynamics permit mitotic bypass, promoting polyploid phenotypes.Cancer letters · 2025Review
- Cells in the Polyaneuploid Cancer Cell State Are Prometastatic.Molecular cancer research : MCR · 2025Article
- Mapping cell-cell fusion at single-cell resolution.bioRxiv : the preprint server for biology · 2025Article
- Targeting autophagy promotes the antitumor effect of radiotherapy on cervical cancer cells.Cancer biology & therapy · 2024Article
- Circulating Polyploid Giant Cancer Cells, a Potential Prognostic Marker in Patients with Carcinoma.International journal of molecular sciences · 2024Article
- Metabolic reprogramming of poly(morpho)nuclear giant cells determines glioblastoma recovery from doxorubicin-induced stress.Journal of translational medicine · 2024Article
- Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.