Exploiting tumor cell senescence in anticancer therapy
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Cellular senescence is a physiological process of irreversiblecell-cycle arrest that contributes to various physiological andpathological processes of aging. Whereas replicative senescenceis associated with telomere attrition after repeated cell division,stress-induced premature senescence occurs in response toaberrant oncogenic signaling, oxidative stress, and DNA damagewhich is independent of telomere dysfunction. Recent evidenceindicates that cellular senescence provides a barrier to tumorigenesisand is a determinant of the outcome of cancertreatment. However, the senescence-associated secretory phenotype,which contributes to multiple facets of senescent cancercells, may influence both cancer-inhibitory and cancer-promotingmechanisms of neighboring cells. Conventional treatments,such as chemo- and radiotherapies, preferentially induce prematuresenescence instead of apoptosis in the appropriate cellularcontext. In addition, treatment-induced premature senescencecould compensate for resistance to apoptosis via alternativesignaling pathways. Therefore, we believe that an intensiveeffort to understand cancer cell senescence could facilitatethe development of novel therapeutic strategies for improvingthe efficacy of anticancer therapies. This review summarizesthe current understanding of molecular mechanisms, functions,and clinical applications of cellular senescence for anticancertherapy.
Abstract
Cellular senescence is a physiological process of irreversiblecell-cycle arrest that contributes to various physiological andpathological processes of aging. Whereas replicative senescenceis associated with telomere attrition after repeated cell division,stress-induced premature senescence occurs in response toaberrant oncogenic signaling, oxidative stress, and DNA damagewhich is independent of telomere dysfunction. Recent evidenceindicates that cellular senescence provides a barrier to tumorigenesisand is a determinant of the outcome of cancertreatment. However, the senescence-associated secretory phenotype,which contributes to multiple facets of senescent cancercells, may influence both cancer-inhibitory and cancer-promotingmechanisms of neighboring cells. Conventional treatments,such as chemo- and radiotherapies, preferentially induce prematuresenescence instead of apoptosis in the appropriate cellularcontext. In addition, treatment-induced premature senescencecould compensate for resistance to apoptosis via alternativesignaling pathways. Therefore, we believe that an intensiveeffort to understand cancer cell senescence could facilitatethe development of novel therapeutic strategies for improvingthe efficacy of anticancer therapies. This review summarizesthe current understanding of molecular mechanisms, functions,and clinical applications of cellular senescence for anticancertherapy.
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