Senescence in tumours: evidence from mice and humans

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Abstract
Senescence is a stress response prevalent in the aberrant environment of tumours. Senescent cells are incapable of further proliferation and therefore tumour cell senescence is a brake to tumour progression. A large body of evidence in mouse models indicates that in pre-malignant tumours most cells are senescent, therefore explaining the slow growth and low malignancy of these tumours. There are also examples of senescence in human pre-malignant tumours. A class of tumour suppressors (for example, p53, INK4A and ARF) monitors stress signals, and the activation of these proteins triggers senescence. Their loss or inactivation is associated with impaired senescence, unleashing malignant progression. Malignant tumours, despite their impaired ability to undergo senescence, can still be forced into senescence if crucial oncogenic pathways are disabled or tumour suppressors are restored. Senescent tumour cells are rapidly cleared by immune cells, resulting in efficient tumour regression. Senescence constitutes a new end point that might be relevant for the development of new drugs or prognostic markers and the evaluation of therapeutic treatments.