Emma Hammarlund
Research team manager
Cancer recurrence and lethality are enabled by enhanced survival and reversible cell cycle arrest of polyaneuploid cells
Author
Summary, in English
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.
Department/s
- StemTherapy: National Initiative on Stem Cells for Regenerative Therapy
- EpiHealth: Epidemiology for Health
- LUCC: Lund University Cancer Centre
- Division of Translational Cancer Research
Publishing year
2021
Language
English
Publication/Series
Proceedings of the National Academy of Sciences of the United States of America
Volume
118
Issue
7
Document type
Journal article
Publisher
National Academy of Sciences
Topic
- Cancer and Oncology
Keywords
- drug resistance
- evolution
- metastasis
- tumor microenvironment
- whole-genome doubling
Status
Published
ISBN/ISSN/Other
- ISSN: 1091-6490