Senescence and cancer — role and therapeutic opportunities

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.