Abstract
Standard chemotherapy and radiotherapy are designed to eradicate malignancies by depriving tumor cells of their reproductive potential. Traditionally, it has been assumed that the loss of proliferative potential by cancer cells predominantly involves the triggering of cell death via apoptosis. However, it is becoming clear that cancer cells derived from solid tumors often undergo rapid and widespread induction of senescence following exposure to DNA damaging therapeutic agents. Tumor cells undergoing this accelerated senescence response share several cellular and molecular features with replicatively aged cells, including activation of DNA damage response pathways and a similar senescence-associated secretory pattern. Here, we discuss accelerated senescence in response to chemotherapy and radiation focusing on the potential implications for treatment response, tumor progression, and cancer survivorship. One emerging theme is that the persistence of metabolically active, senescent cells plays an active and diverse role in shaping the tumor microenvironment. There is hope that a better understanding of the molecular mechanisms (1) initiating and maintaining senescence in cancer cells and (2) underlying the senescence-associated bystander effects in tumor and non-tumor cells will lead to the future development of more efficacious and less toxic cancer treatments.
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Acknowledgements
This work was supported by a National Institutes of Health KO1 CA105050-01A131, a Department of Defense BCRP Concept Award (BC085416), and the Department of Pathology at Virginia Commonwealth University (to LWE). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or DOD. We regret that we were unable to cite all relevant studies in the literature. Due to the fact that, in several circumstances, no appropriate reviews were available, it was necessary to select one or two primary papers while other equally relevant papers were omitted.
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Bristol, M.L., Elmore, L.W. (2013). Chemotherapy- and Radiation-Induced Accelerated Senescence: Implications for Treatment Response, Tumor Progression and Cancer Survivorship. In: Hayat, M. (eds) Tumor Dormancy, Quiescence, and Senescence, Volume 1. Tumor Dormancy and Cellular Quiescence and Senescence, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5958-9_20
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