TY - JOUR
T1 - Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy
AU - Pienta, K. J.
AU - Hammarlund, E. U.
AU - Austin, R. H.
AU - Axelrod, R.
AU - Brown, J. S.
AU - Amend, S. R.
N1 - Funding Information:
The authors dedicate this article to the memory of Donald S. Coffey, PhD, who inspired us all to think out-of-the-box, conduct multidisciplinary research, and perform team science to understand and defeat the complexity of cancer. This work was funded by Swedish Research Council grant 2019-05254, The Crafoord Foundation, and the European Union's Horizon 2020 research and innovation program (Starting Grant No 949538) to E.U. Hammarlund; NIH/NCIR01CA170595, and NIH/NCI U54CA143970-05 to J.S. Brown; US Department of Defense CDMRP/PCRP (W81XWH-20-10353), the Patrick C. Walsh Prostate Cancer Research Fund and the Prostate Cancer Foundation to S.R. Amend; and NCI grantsU54CA143803,CA163124,CA093900, andCA143055, and the Prostate Cancer Foundation to K.J. Pienta. This work was also supported by the William and Carolyn Stutt Research Fund, Ronald Rose,MC Dean, Inc. William and Marjorie Springer, Mary and Dave Stevens,Louis Dorfman, the Jones Family Foundation, Timothy Hanson, and the David and June Trone Family Foundation. Art in Figs. 1,3,4,5,6, and 8 generated with Servier Medical Art, CC BY 3.0.
Funding Information:
The authors dedicate this article to the memory of Donald S. Coffey, PhD, who inspired us all to think out-of-the-box, conduct multidisciplinary research, and perform team science to understand and defeat the complexity of cancer. This work was funded by Swedish Research Council grant 2019-05254 , The Crafoord Foundation , and the European Union's Horizon 2020 research and innovation program (Starting Grant No 949538 ) to E.U. Hammarlund; NIH/NCI R01CA170595 , and NIH/NCI U54CA143970-05 to J.S. Brown; US Department of Defense CDMRP/PCRP ( W81XWH-20-10353 ), the P atrick C. Walsh Prostate Cancer Research Fund and the P rostate Cancer Foundation to S.R. Amend; and NCI grants U54CA143803, CA163124, CA093900, and CA143055, and the Prostate Cancer Foundation to K.J. Pienta. This work was also supported by the William and Carolyn Stutt Research Fund , Ronald Rose, MC Dean, Inc., W illiam and Marjorie Springer , Mary and Dave Stevens, Louis Dorfman, the J ones Family Foundation, T imothy Hanson , and the David and June Trone Family Foundation . Art in Figs. 1,3,4,5,6, and 8 generated with Servier Medical Art, CC BY 3.0.
Publisher Copyright:
© 2020 The Author(s)
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Convergent evolution
KW - Lethal cancer
KW - Polyploid giant cancer cells
KW - Therapeutic resistance
KW - Whole genome doubling
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U2 - 10.1016/j.semcancer.2020.11.016
DO - 10.1016/j.semcancer.2020.11.016
M3 - Review article
C2 - 33276091
AN - SCOPUS:85097755342
VL - 81
SP - 145
EP - 159
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
SN - 1044-579X
ER -