Epub 2019 Aug 10.Methods Mol Biol. The SASP of senescent cells contributes to many side effects, including cardiac dysfunction, fatigue, bone loss, and physical decline in treated patients.Targeted removal of senescent cells (senolysis) is an emerging strategy in cancer treatments, particularly in combination with more traditional anticancer interventions [Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.Exploiting interconnected synthetic lethal interactions between PARP inhibition and cancer cell reversible senescence.Targeting BCL-xL improves the efficacy of bromodomain and extra-terminal protein inhibitors in triple-negative breast cancer by eliciting the death of senescent cells.Targeting BCL-xL improves the efficacy of bromodomain and extra-terminal protein inhibitors in triple-negative breast cancer by eliciting the death of senescent cells.mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation.mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype.Concurrent and sequential administration of chemotherapy and the mammalian target of rapamycin inhibitor temsirolimus in human cancer cells and xenografts.Inducing and exploiting vulnerabilities for the treatment of liver cancer.The HDAC inhibitor panobinostat was also shown to promote senolysis of chemotherapy-treated NSCLC and head and neck squamous cell carcinoma (HNSCC) cell lines (A549, H460; UMSCC47, FaDu) [A novel indication for panobinostat as a senolytic drug in NSCLC and HNSCC.Identification and characterization of cardiac glycosides as senolytic compounds.mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation.Metformin decreases the dose of chemotherapy for prolonging tumor remission in mouse xenografts involving multiple cancer cell types.Together with potentiating cancer cell elimination, senotherapies have the potential to improve the healthspan of cancer patients. Because of its lack of specificity, radiotherapy can be used to treat numerous cancers including lymphoma, soft tissue sarcomas, central nervous system tumors, and a wide range of carcinomas (lung, prostate, skin, breast, head and neck, bladder) [Cancer and radiation therapy: current advances and future directions.A senescence-like phenotype distinguishes tumor cells that undergo terminal proliferation arrest after exposure to anticancer agents.Promotion of cellular senescence by THG-1/TSC22D4 knockout through activation of JUNB.p53-dependent accelerated senescence induced by ionizing radiation in breast tumour cells.p53-dependent accelerated senescence induced by ionizing radiation in breast tumour cells.An accelerated senescence response to radiation in wild-type p53 glioblastoma multiforme cells.IR is commonly used to prematurely induce senescence in cells Cellular senescence promotes adverse effects of chemotherapy and cancer relapse.Radiation-induced senescence-like phenotype in proliferating and plateau-phase vascular endothelial cells.Ionizing irradiation inhibits keloid fibroblast cell proliferation and induces premature cellular senescence.mTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation.Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice.The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs.Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence.An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.Sublethal whole-body irradiation causes progressive premature frailty in mice.Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status.CDK4 and CDK6 are critical factors for the cell cycle transition from G1 to S phase [Specific protection against breast cancers by cyclin D1 ablation.Requirement for CDK4 kinase function in breast cancer.Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma.Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma.A combination CDK4/6 and IGF1R inhibitor strategy for Ewing sarcoma.Overcoming therapeutic resistance in HER2-positive breast cancers with CDK4/6 inhibitors.Genomic aberrations that activate D-type cyclins are associated with enhanced sensitivity to the CDK4 and CDK6 inhibitor abemaciclib.Preclinical characterization of abemaciclib in hormone receptor positive breast cancer.Lysosomal trapping of palbociclib and its functional implications.Lysosomal trapping of palbociclib and its functional implications.Stromal senescence by prolonged CDK4/6 inhibition potentiates tumor growth.Lysosomal trapping of palbociclib and its functional implications.The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype.p16INK4a can initiate an autonomous senescence program.Mechanistic investigation of bone marrow suppression associated with palbociclib and its differentiation from cytotoxic chemotherapies.Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors.Induction of therapeutic senescence in vemurafenib-resistant melanoma by extended inhibition of CDK4/6.5-Aza-2′-deoxycytidine (5-aza) is an inhibitor of DNA methyltransferase (DNMT), which can cause global demethylation of CpG-enriched promoters or enhancers [Stress chaperones, mortalin, and Pex19p mediate 5-aza-2′ deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway.Stress chaperones, mortalin, and Pex19p mediate 5-aza-2′ deoxycytidine-induced senescence of cancer cells by DNA methylation-independent pathway.Premature senescence induced by DNA demethylating agent (decitabine) as therapeutic option for malignant pleural mesothelioma.Induction of senescence in cancer cells by 5′-aza-2′-deoxycytidine: bioinformatics and experimental insights to its targets.Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence.Induction of polyploidy by histone deacetylase inhibitor: a pathway for antitumor effects.Epigenetic modulation of gene expression of human leukemia cell lines – induction of cell death and senescence.Effects of novel HDAC inhibitors on urothelial carcinoma cells.Unlocking the chromatin of adenoid cystic carcinomas using HDAC inhibitors sensitize cancer stem cells to cisplatin and induces tumor senescence.Suberoylanilide hydroxamic acid (SAHA) causes tumor growth slowdown and triggers autophagy in glioblastoma stem cells.Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent.Histone deacetylase inhibitors induce a senescence-like state in human cells by a p16-dependent mechanism that is independent of a mitotic clock.As immunotherapeutic drugs mediate immune-mediated cancer cell apoptosis, it is possible that the SASP could be a modulator of this process.
SASP factors are able to potentiate various aspects of tumorigenesis, including proliferation, metastasis, and immunosuppression. The sooner these
CSLCs are rare quiescent cells.
Riuximab is a CD20 targeting antibody used to treat leukemia and lymphoma. Removal of chemotherapy-induced systemic senescent cells reduced the burden of inflammatory SASP factors and myelosuppression, thus preventing physical decline, frailty, and cardiac dysfunctions [Cellular senescence promotes adverse effects of chemotherapy and cancer relapse.Inhibition of the stromal p38MAPK/MK2 pathway limits breast cancer metastases and chemotherapy-induced bone loss.Cellular senescence promotes adverse effects of chemotherapy and cancer relapse.p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype.An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA.Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status.Sublethal whole-body irradiation causes progressive premature frailty in mice.Cancer therapy is effective in inhibiting cancer progression but can induce premature cellular senescence in normal or cancer cells.
Comments Moreover, the accumulation and persistence of therapy-induced senescent cells can promote tissue dysfunction and the early onset of various age-related symptoms in treated cancer patients. Paradoxically, senescent cells develop an inflammatory secretome, termed the senescence-associated secretory phenotype, which is implicated in age-related pathologies including cancer.
"Senescent cells are effectively the opposite of stem cells, which have an unlimited potential for self-renewal or division," Delfarah said.
New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Tonnessen-Murray CA(1), Frey WD(1), Rao SG(1), Shahbandi A(1), Ungerleider NA(1), Olayiwola JO(1), Murray LB(1), Vinson BT(2), Chrisey DB(2), Lord CJ(3), Jackson JG(4). inappropriate behavior are likely to be deleted.
Cellular senescence is a potent tumor-suppressive program that prevents neoplastic events. Senescent cells secrete a collection of proinflammatory factors collectively termed the senescence-associated secretory phenotype (SASP).