An Oncogene-Induced DNA Damage Model for Cancer Development

  title={An Oncogene-Induced DNA Damage Model for Cancer Development},
  author={Thanos D Halazonetis and Vassilis G. Gorgoulis and Jiri Bartek},
  pages={1352 - 1355}
Of all types of DNA damage, DNA double-strand breaks (DSBs) pose the greatest challenge to cells. One might have, therefore, anticipated that a sizable number of DNA DSBs would be incompatible with cell proliferation. Yet recent experimental findings suggest that, in both precancerous lesions and cancers, activated oncogenes induce stalling and collapse of DNA replication forks, which in turn leads to formation of DNA DSBs. This continuous formation of DNA DSBs may contribute to the genomic… 

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The imposition of low levels of genotoxic stress on AML derived leukemic cells rendered them unable to self-renew and instead promoted their differentiation to mature myeloid cells.

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The latest preclinical and clinical developments in cancer therapy based on the current knowledge of DSB signalling and repair are summarized, with a special focus on the combination of small molecule inhibitors with synthetic lethality approaches.

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Critical DNA damaging pathways in tumorigenesis.

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