Senescence in tumours: evidence from mice and humans - PubMed (original) (raw)

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Senescence in tumours: evidence from mice and humans

Manuel Collado et al. Nat Rev Cancer. 2010 Jan.

Abstract

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.

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Figures

Figure 1

Figure 1

Signalling pathways and oncogenes (marked by a red asterisk) whose activation leads to senescence induction in vivo.

Figure 2

Figure 2

Tumour suppressors can be grouped into two categories depending on their effect on senescence. Some tumour suppressors (at the top of the cascade, i.e. “upstream of oncogenes”) prevent excessive oncogenic signalling and their deletion in normal cells triggers senescence. Other tumour suppressors (“downstream of oncogenes”) sense excessive oncogenic signalling and induce senescence, and their absence in tumour cells allows progression to malignancy.

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