Exploiting senescence for the treatment of cancer

Nature reviews. Cancer, Год журнала: 2022, Номер 22(6), С. 340 - 355

Опубликована: Март 3, 2022

Язык: Английский

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Senescence and cancer — role and therapeutic opportunities

Nature Reviews Clinical Oncology, Год журнала: 2022, Номер 19(10), С. 619 - 636

Опубликована: Авг. 31, 2022

Язык: Английский

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Strategies for targeting senescent cells in human disease

Nature Aging, Год журнала: 2021, Номер 1(10), С. 870 - 879

Опубликована: Окт. 7, 2021

Язык: Английский

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Cellular senescence: a key therapeutic target in aging and diseases

Journal of Clinical Investigation, Год журнала: 2022, Номер 132(15)

Опубликована: Июль 31, 2022

Cellular senescence is a hallmark of aging defined by stable exit from the cell cycle in response to cellular damage and stress. Senescent cells (SnCs) can develop characteristic pathogenic senescence-associated secretory phenotype (SASP) that drives secondary disrupts tissue homeostasis, resulting loss repair regeneration. The use transgenic mouse models which SnCs be genetically ablated has established key role for driving age-related disease. Importantly, senotherapeutics have been developed pharmacologically eliminate SnCs, termed senolytics, or suppress SASP other markers senescence, senomorphics. Based on extensive preclinical studies as well small clinical trials demonstrating benefits senotherapeutics, multiple are under way. This Review discusses diseases, strategies target approaches discover advances senolytics.

Язык: Английский

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Blocking PD-L1–PD-1 improves senescence surveillance and ageing phenotypes

Nature, Год журнала: 2022, Номер 611(7935), С. 358 - 364

Опубликована: Ноя. 2, 2022

Язык: Английский

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Immune ageing at single-cell resolution

Nature reviews. Immunology, Год журнала: 2021, Номер 22(8), С. 484 - 498

Опубликована: Ноя. 23, 2021

Язык: Английский

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Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis

Nature, Год журнала: 2022, Номер 610(7931), С. 356 - 365

Опубликована: Окт. 5, 2022

Язык: Английский

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p21 produces a bioactive secretome that places stressed cells under immunosurveillance

Science, Год журнала: 2021, Номер 374(6567)

Опубликована: Окт. 28, 2021

Immune cells identify and destroy damaged to prevent them from causing cancer or other pathologies by mechanisms that remain poorly understood. Here, we report the cell-cycle inhibitor p21 places under immunosurveillance establish a biological timer mechanism controls cell fate. activates retinoblastoma protein (Rb)–dependent transcription at select gene promoters generate complex bioactive secretome, termed p21-activated secretory phenotype (PASP). The PASP includes chemokine CXCL14, which promptly attracts macrophages. These macrophages disengage if normalize within 4 days, but induction persists, they polarize toward an M1 lymphocytes mount cytotoxic T response eliminate target cells, including preneoplastic cells. Thus, concurrently induces proliferative arrest of duress.

Язык: Английский

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The heterogeneity of cellular senescence: insights at the single-cell level

Trends in Cell Biology, Год журнала: 2022, Номер 33(1), С. 9 - 17

Опубликована: Май 20, 2022

Язык: Английский

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The roles and mechanisms of senescence-associated secretory phenotype (SASP): can it be controlled by senolysis?

Inflammation and Regeneration, Год журнала: 2022, Номер 42(1)

Опубликована: Апрель 2, 2022

Abstract Cellular senescence is a state of irreversible cell cycle arrest that can be induced by variety potentially oncogenic stimuli, including DNA damage. Hence, has long been considered to suppress tumorigenesis, acting as guardian homeostasis. However, recent studies have revealed senescent cells exhibit the secretion series inflammatory cytokines, chemokines, growth factors, and matrix remodeling factors alter local tissue environment contribute chronic inflammation cancer. This phenotype termed senescence-associated secretory (SASP) observed not only in cultured vitro but also vivo . Recently, physiological pathological roles SASP increasingly clarified. Notably, several reported intrinsic mechanism factor production predominantly mediated through activation cGAS-STING (cyclic GMP-AMP synthase-stimulator interferon genes) pathway aberrantly accumulated fragments from nucleus cells. In contrast, various extrinsic triggers exist vivo, for example, induction hepatic stellate tumor microenvironment obesity-associated liver cancer translocated gut microbial metabolites. strategy elimination (senolysis) attracted increasing attention. Thus, role effects outcomes senolysis will discussed this review.

Язык: Английский

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