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The genetics of the p53 pathway, apoptosis and cancer therapy

Abstract

The p53 pathway has been shown to mediate cellular stress responses; p53 can initiate DNA repair, cell-cycle arrest, senescence and, importantly, apoptosis. These responses have been implicated in an individual's ability to suppress tumour formation and to respond to many types of cancer therapy. Here we focus on how best to use knowledge of this pathway to tailor current therapies and develop novel ones. Studies of the genetics of p53 pathway components — in particular p53 itself and its negative regulator MDM2 — in cancer cells has proven useful in the development of targeted therapies. Furthermore, inherited single nucleotide polymorphisms in p53 pathway genes could serve a similar purpose.

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Figure 1: Cancer therapy.
Figure 2: The p53 pathway, somatic genetics and cancer therapeutics.
Figure 3: The p53 pathway, polymorphisms, apoptosis and cancer therapy.
Figure 4: The NCI60 human tumour cell line anticancer drug screen, somatic genetics, SNPs and the p53 pathway: an analysis.

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Acknowledgements

The authors would like to acknowledge the NCI-DCTD Repository Molecular Characterization Program for the development of the 60 cell line screening panel, their molecular characterization and the generous contribution of genomic DNA from the NCI60 panel of cell lines.

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Correspondence to Gareth L. Bond.

Supplementary information

Supplementary information S1 (table)

p53 stress response genes (PDF 365 kb)

Supplementary information S2 (table)

Six SNPs with allelic differences in p53-dependent drug responses (PDF 156 kb)

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Vazquez, A., Bond, E., Levine, A. et al. The genetics of the p53 pathway, apoptosis and cancer therapy. Nat Rev Drug Discov 7, 979–987 (2008). https://doi.org/10.1038/nrd2656

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