Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy

K. J. Pienta, E. U. Hammarlund, R. H. Austin, R. Axelrod, J. S. Brown, S. R. Amend

Research output: Contribution to journalReview articlepeer-review

30 Scopus citations


Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.

Original languageEnglish (US)
Pages (from-to)145-159
Number of pages15
JournalSeminars in Cancer Biology
StatePublished - Jun 2022

All Science Journal Classification (ASJC) codes

  • Cancer Research


  • Convergent evolution
  • Lethal cancer
  • Polyploid giant cancer cells
  • Therapeutic resistance
  • Whole genome doubling


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