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Open AccessJournal ArticleDOI

Senescence in tumours: evidence from mice and humans

Manuel Collado, +1 more
- 01 Jan 2010 - 
- Vol. 10, Iss: 1, pp 51-57
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TLDR
The importance of cellular senescence, which is a stress response that stably blocks proliferation, is increasingly being recognized and translating these concepts to clinical oncology remains a challenge.
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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Hallmarks of cancer: the next generation.

TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
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Senescence-Associated Secretory Phenotypes Reveal Cell-Nonautonomous Functions of Oncogenic RAS and the p53 Tumor Suppressor

TL;DR: Coppe et al. as mentioned in this paper showed that human cells induced to senesce by genotoxic stress secrete myriad factors associated with inflammation and malignancy, including interleukin (IL)-6 and IL-8.
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Aging, Cellular Senescence, and Cancer

TL;DR: The idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence is discussed.
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The essence of senescence

TL;DR: The various features of cellular senescence are reviewed and their contribution to tumor suppression is discussed and the power and limitations of the biomarkers currently used to identify senescent cells in vitro and in vivo are highlighted.
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Cellular senescence: from physiology to pathology.

TL;DR: In cancer and during active tissue repair, pro-senescent therapies contribute to minimize the damage by limiting proliferation and fibrosis, respectively, and antisenescent therapies may help to eliminate accumulated senescent cells and to recover tissue function.
References
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Journal ArticleDOI

The serial cultivation of human diploid cell strains.

TL;DR: A consideration of the cause of the eventual degeneration of these strains leads to the hypothesis that non-cumulative external factors are excluded and that the phenomenon is attributable to intrinsic factors which are expressed as senescence at the cellular level.
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A biomarker that identifies senescent human cells in culture and in aging skin in vivo

TL;DR: It is shown that several human cells express a beta-galactosidase, histochemically detectable at pH 6, upon senescence in culture, which provides in situ evidence that senescent cells may exist and accumulate with age in vivo.
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Oncogenic ras Provokes Premature Cell Senescence Associated with Accumulation of p53 and p16INK4a

TL;DR: It is shown that expression of oncogenic ras in primary human or rodent cells results in a permanent G1 arrest, and that the onset of cellular senescence does not simply reflect the accumulation of cell divisions, but can be prematurely activated in response to an onCogenic stimulus.
Journal ArticleDOI

Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

TL;DR: It is indicated that p53 loss can be required for the maintenance of aggressive carcinomas, and illustrates how the cellular senescence program can act together with the innate immune system to potently limit tumour growth.
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