Therapy-induced senescence in cancer.
Open accessAbstract
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.
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Treatment with some anticancer agents, chemotherapeutic drugs or ionizing radiation provokes therapy-induced senescence (TIS) in tumor cells.
“Recent studies have demonstrated that treatment with some anticancer agents, chemotherapeutic drugs or ionizing radiation provoke “therapy-induced senescence (TIS)” in tumor cells (Di Micco et al., 2006; Ewald et al., 2010; Dörr et al., 2013; Toso et al., 2014; Petrova et al., 2016; Dabrowska et al., 2018; Saleh et al., 2018, 2019; Mikuła-Pietrasik et al., 2020).”
From Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype (2021) · cites this paper as Ewald et al., 2010
Failsafe cellular senescence occurs in response to oncogene activation, oncosuppressor inactivation, and sublethal insults including telomere shortening, DNA damage, mitochondrial dysfunction, defective/stalled DNA replication, and epigenetic, lysosomal, mechanical, metabolic, mitotic, oxidative, or proteotoxic challenges.
“In particular, this failsafe cellular senescence reportedly occurs in response to (1) potentially carcinogenic events including oncogene activation or oncosuppressor gene inactivation; and (2) several sublethal cellular insults, including telomere shortening, DNA damage, mitochondrial dysfunction, defective/stalled DNA replication and epigenetic, lysosomal, mechanical, metabolic, mitotic, ox”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [959]
Some tumor cells can enter senescence in response to DNA damaging therapies.
“some tumor cells can enter senescence in response to DNA damaging therapies [363,364].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [363]
The main advantage of the senescence response caused by traditional chemotherapeutic agents is that cancer cell senescence can be induced with lower doses than those used to cause cancer cell death, thus possibly reducing adverse side effects.
“The main advantage of the senescence response caused by traditional chemotherapeutic agents is that cancer cell senescence can be induced with lower doses than those used to cause cancer cell death, thus possibly reducing the adverse side effects [363,367].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [363]
Persistence of senescent tumor cells can be a source of chronic inflammation and resistance to chemotherapy.
“Consequently, persistence of senescent tumor cells can be a source of chronic inflammation and of resistance to chemotherapy [363].”
From Mechanisms and Regulation of Cellular Senescence (2021) · cites this paper as [363]
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- Authors
- Ewald, J. A., Desotelle, J. A., Wilding, G., & Jarrard, D. F.
- Affiliations
- University of Wisconsin–Madison (US)
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-10-20
- Volume
- 102
- Issue
- 20
- Pages
- 1536-1546
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- PMC
- PMC2957429
- OpenAlex
- W2136380412
- Cited by
- 824
- References
- 100
- Citations by year
- 2026: 32 · 2025: 69 · 2024: 62 · 2023: 75 · 2022: 83 · 2021: 74 · 2020: 85 · 2019: 66 · 2018: 49 · 2017: 46 · 2016: 33 · 2015: 43 · 2014: 29 · 2013: 30 · 2012: 29
- FWCI
- 2.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- U.S. Department of Defense
- National Institutes of Health
- National Cancer Institute (R01CA97131, T32CA009681, R01CA097131)
- National Institute of Diabetes and Digestive and Kidney Diseases (P50DK065303)
- DOD Prostate Cancer Research Program
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- therapy-induced senescence, cellular senescence, cancer therapy, senescence biomarkers, p53, retinoblastoma protein, radiation-induced senescence, anticancer agents, tumor-specific immunity
- MeSH terms
- Animals, Humans, Neoplasms, Quality of Life, Time Factors, Cellular Senescence, Apoptosis, Oxidative Stress, Cell Proliferation
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