Senescence and cancer - role and therapeutic opportunities

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 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.

Automated summary

This review discusses the mechanisms of senescent cells in both anti-cancer and pro-cancer effects, and describes the potential of various senescence-based therapies in oncology.