The Dormancy Dilemma: Quiescence versus Balanced Proliferation
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Griffith_The dormancy.pdf
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Author(s)
Wells, Alan
Griffith, Linda G.
Wells, Jakob Z.
Taylor, Donald P.
Date Issued
June 2013
Journal
Cancer Research
Publisher
American Association for Cancer Research
Citation
Wells, A., L. Griffith, J. Z. Wells, and D. P. Taylor. “The Dormancy Dilemma: Quiescence Versus Balanced Proliferation.” Cancer Research 73, no. 13 (June 21, 2013): 3811–3816.
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Author's final manuscript
Abstract
Metastatic dissemination with subsequent clinical outgrowth leads to the greatest part of morbidity and mortality from most solid tumors. Even more daunting is that many of these metastatic deposits silently lie undetected, recurring years to decades after primary tumor extirpation by surgery or radiation (termed metastatic dormancy). As primary tumors are frequently curable, a critical focus now turns to preventing the lethal emergence from metastatic dormancy. Current carcinoma treatments include adjuvant therapy intended to kill the cryptic metastatic tumor cells. Because such standard therapies mainly kill cycling cells, this approach carries an implicit assumption that metastatic cells are in the mitogenic cycle. Thus, the pivotal question arises as to whether clinically occult micrometastases survive in a state of balanced proliferation and death, or whether these cells undergo at least long periods of quiescence marked by cell-cycle arrest. The treatment implications are thus obvious—if the carcinoma cells are cycling then therapies should target cycling cells, whereas if cells are quiescent then therapies should either maintain dormancy or be toxic to dormant cells. Because this distinction is paramount to rational therapeutic development and administration, we investigated whether quiescence or balanced proliferation is the most likely etiology underlying metastatic dormancy. We recently published a computer simulation study that determined that balanced proliferation is not the likely driving force and that quiescence most likely participates in metastatic dormancy. As such, a greater emphasis on developing diagnostics and therapeutics for quiescent carcinomas is needed.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
https://doi.org/10.1158/0008-5472.can-13-0356
