Senescence and cancer — role and therapeutic opportunities
By C. Schmitt, Boshi Wang, M. Demaria. Nature Reviews Clinical Oncology, 2022
632 citations recorded by the source corpus.
Cellular senescence is a state of stable, terminal cell cycle arrest associated with various macromolecular changes and a hypersecretory, pro-inflammatory phenotype. Entry of cells into senescence can act as a barrier to tumorigenesis and, thus, could in principle constitute a desired outcome for any anticancer therapy. Paradoxically, studies published in the past decade have demonstrated that, in certain conditions and contexts, malignant and non-malignant cells with lastingly persistent senescence can acquire pro-tumorigenic properties. In this Review, we first discuss the major mechanisms involved in the antitumorigenic functions of senescent cells and then consider the cell-intrinsic and cell-extrinsic factors that participate in their switch towards a tumour-promoting role, providing an overview of major translational and emerging clinical findings. Finally, we comprehensively describe various senolytic and senomorphic therapies and their potential to benefit patients with cancer. The entry of cells into senescence can act as a barrier to tumorigenesis; however, in certain contexts senescent malignant and non-malignant cells can acquire pro-tumorigenic properties. The authors of this Review discuss the cell-intrinsic and cell-extrinsic mechanisms involved in both the antitumorigenic and tumour-promoting roles of senescent cells, and describe the potential of various senolytic and senomorphic therapeutic approaches in oncology. Cellular senescence is a natural barrier to tumorigenesis; senescent cells are widely detected in premalignant lesions from patients with cancer. Cellular senescence is induced by anticancer therapy and can contribute to some treatment-related adverse events (TRAEs). Senescent cells exert both protumorigenic and antitumorigenic effects via cell-autonomous and paracrine mechanisms. Pharmacological modulation of senescence-associated phenotypes has the potential to improve therapy efficacy and reduce the incidence of TRAEs. Cellular senescence is a natural barrier to tumorigenesis; senescent cells are widely detected in premalignant lesions from patients with cancer. Cellular senescence is induced by anticancer therapy and can contribute to some treatment-related adverse events (TRAEs). Senescent cells exert both protumorigenic and antitumorigenic effects via cell-autonomous and paracrine mechanisms. Pharmacological modulation of senescence-associated phenotypes has the potential to improve therapy efficacy and reduce the incidence of TRAEs.
Subfields: Biotechnology, Molecular Biology, Physiology
View Paper: https://www.semanticscholar.org/paper/d0cb688d8e8bec228f2d4e50e869ff2d52b6636a
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Citations in the corpus
- The senescence-associated secretory phenotype and its physiological and pathological implications (2024, neutral): “…proliferation arrest; oncogene-induced senescence (OIS) 3 , for cells overexpressing an onco-gene, primarily RAS; therapy-induced senescence (TIS) 4,5 , for cells exposed to high but non-lethal doses of drugs or chemicals; mitochondrial dysfunction-induced senescence (MiDAS) 6 , for cells…”
- Aging and aging-related diseases: from molecular mechanisms to interventions and treatments (2022, background): “In the therapy-induced senescence model, cells undergoing senescence regain proliferative properties through reversibility of senescence, or acquire senescence-associated stemness by reprogramming mechanisms and turn into highly aggressive tumors, which drive tumor recurrence and progression.(485) T”