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Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors.

Mendes-Pereira, AM; Martin, SA; Brough, R; McCarthy, A; Taylor, JR; Kim, J-S; Waldman, T; ... Ashworth, A; + view all (2009) Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med , 1 (6-7) pp. 315-322. 10.1002/emmm.200900041.

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Abstract

The tumour suppressor gene, phosphatase and tensin homolog (PTEN), is one of the most commonly mutated genes in human cancers. Recent evidence suggests that PTEN is important for the maintenance of genome stability. Here, we show that PTEN deficiency causes a homologous recombination (HR) defect in human tumour cells. The HR deficiency caused by PTEN deficiency, sensitizes tumour cells to potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP), both in vitro and in vivo. PARP inhibitors are now showing considerable promise in the clinic, specifically in patients with mutations in either of the breast cancer susceptibility genes BRCA1 or BRCA2. The data we present here now suggests that the clinical assessment of PARP inhibitors should be extended beyond those with BRCA mutations to a larger group of patients with PTEN mutant tumours.

Type: Article
Title: Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors.
Location: England
DOI: 10.1002/emmm.200900041
Keywords: Animals, Antimetabolites, Antineoplastic, BRCA1 Protein, BRCA2 Protein, Cell Line, Tumor, Cell Survival, Female, Humans, Mice, Mice, Nude, Mutation, Neoplasms, PTEN Phosphohydrolase, Phthalazines, Piperazines, Poly(ADP-ribose) Polymerase Inhibitors, Recombination, Genetic
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: http://discovery.ucl.ac.uk/id/eprint/1349131
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