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Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy
K J Pienta1, E U Hammarlund2, R H Austin3
1The Brady Urological Institute and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins School of Medicine, Baltimore, MD 21287, United States.
Seminars in Cancer Biology
|December 4, 2020
Summary
Large cancer cells, previously ignored, utilize whole genome doubling for survival under stress. These polyaneuploid cancer cells (PACCs) drive therapeutic resistance, cancer recurrence, and lethality.
Area of Science:
- Oncology
- Cell Biology
- Genetics
Background:
- Unusually large cancer cells with abnormal nuclei have been observed for over 150 years.
- These cells were historically dismissed as non-functional, senescent, or dying.
- Cell enlargement and genome doubling are conserved mechanisms across organisms for stress adaptation.
Purpose of the Study:
- To investigate the role of large, polyploid cancer cells in cancer progression.
- To understand the mechanisms of polyploidization in cancer.
- To identify the source of therapeutic resistance and cancer lethality.
Main Methods:
- Comparative analysis of polyploidization mechanisms in various organisms and non-transformed tissues.
- Examination of conserved survival programs utilized by cancer cells.
Main Results:
- Cancer cells employ whole genome doubling and proliferation pausing as a survival strategy under stress.
- These polyaneuploid cancer cells (PACCs) are linked to therapeutic resistance.
- PACCs are identified as the cause of cancer recurrence and lethality.
Conclusions:
- Polyaneuploid cancer cells (PACCs) are not merely non-functional but represent a critical survival mechanism.
- Understanding PACCs is crucial for developing strategies to overcome therapeutic resistance.
- PACCs are a key driver of cancer recurrence and fatal outcomes.
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