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Intrinsic tumour suppression

Nature volume 432, pages 307315 (18 November 2004) | Download Citation

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Abstract

Mutations that drive uncontrolled cell-cycle progression are requisite events in tumorigenesis. But evolution has installed in the proliferative programmes of mammalian cells a variety of innate tumour-suppressive mechanisms that trigger apoptosis or senescence, should proliferation become aberrant. These contingent processes rely on a series of sensors and transducers that act in a coordinated network to target the machinery responsible for apoptosis and cell-cycle arrest at different points. Although oncogenic mutations that disable such networks can have profound and varied effects on tumour evolution, they may leave intact latent tumour-suppressive potential that can be harnessed therapeutically.

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Acknowledgements

We thank members of the Lowe and Evan laboratories for discussions, and M. Hemann, D. Burgess and M. McCurrach for critical readings of the manuscript. S. L. is supported by an NFCR-AACR research professorship and grants from the National Institutes of Health and the Leukemia and Lymphoma Society, E. C. is supported by a postdoctoral training fellowship from the National Cancer Institute, and G. E. is supported by grants from the NIH, the Juvenile Diabetes Foundation and the Brain Tumor Society.

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Affiliations

  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA

    • Scott W. Lowe
    •  & Enrique Cepero
  2. Cancer Research Institute, University of California at San Francisco, San Francisco, California 94143, USA

    • Gerard Evan

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  2. Search for Enrique Cepero in:

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Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Scott W. Lowe.

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https://doi.org/10.1038/nature03098

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