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- Title
Therapy-Induced Senescence in Cancer.
- Authors
Ewald, Jonathan A.; Desotelle, Joshua A.; Wilding, George; Jarrard, David F.
- Abstract
Cellular senescence is a response to nonlethal stress that results in persistent cytostasis with a distinct morphological and biochemical phenotype. The senescence phenotype, detected in tumors through the expression of mRNA and protein markers, can be generated in cancer cells lacking functional p53 and retinoblastoma protein. Current research suggests that therapy-induced senescence (TIS) represents a novel functional target that may improve cancer therapy. TIS can be induced in immortal and transformed cancer cells by selected anticancer compounds or radiation, and accumulating data indicate that TIS may produce reduced toxicity-related side effects and increased tumor-specific immune activity. This review examines the current status of TIS-regulated mechanisms, agents, and senescence biomarkers with the goal of encouraging further development of this approach to cancer therapy. Remaining hurdles include the lack of efficient senescence-inducing agents and incomplete biological data on tumor response. The identification of additional compounds and other targeted approaches to senescence induction will further the development of TIS in the clinical treatment of cancer.
- Subjects
PHYSIOLOGICAL stress; MORPHOLOGY; TUMORS; MESSENGER RNA; PROTEINS; CANCER cells
- Publication
JNCI: Journal of the National Cancer Institute, 2010, Vol 102, Issue 20, p1536
- ISSN
0027-8874
- Publication type
Article
- DOI
10.1093/jnci/djq364