Senescence in tumours: evidence from mice and humans

Oncogene-induced senescence was first seen in cultured cells. However, since the initialin vitro observation of this phenomenon, it has been shown to occur in both mouse and human tumours. What do we know about tumour cell senescence in vivo, and how might this be exploited therapeutically? The importance of cellular senescence, which is a stress response that stably blocks proliferation, is increasingly being recognized. Senescence is prevalent in pre-malignant tumours, and progression to malignancy requires evading senescence. Malignant tumours, however, may still undergo senescence owing to interventions that restore tumour suppressor function or inactivate oncogenes. Senescent tumour cells can be cleared by immune cells, which may result in efficient tumour regression. Standard chemotherapy also has the potential to induce senescence, which may partly underlie its therapeutic activity. Although these concepts are well supported in mouse models, translating them to clinical oncology remains a challenge.