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Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors

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...

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Autores principales: Mendes-Pereira, Ana M, Martin, Sarah A, Brough, Rachel, McCarthy, Afshan, Taylor, Jessica R, Kim, Jung-Sik, Waldman, Todd, Lord, Christopher J, Ashworth, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378149/
https://www.ncbi.nlm.nih.gov/pubmed/20049735
http://dx.doi.org/10.1002/emmm.200900041
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author Mendes-Pereira, Ana M
Martin, Sarah A
Brough, Rachel
McCarthy, Afshan
Taylor, Jessica R
Kim, Jung-Sik
Waldman, Todd
Lord, Christopher J
Ashworth, Alan
author_facet Mendes-Pereira, Ana M
Martin, Sarah A
Brough, Rachel
McCarthy, Afshan
Taylor, Jessica R
Kim, Jung-Sik
Waldman, Todd
Lord, Christopher J
Ashworth, Alan
author_sort Mendes-Pereira, Ana M
collection PubMed
description 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.
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spelling pubmed-33781492012-09-17 Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors Mendes-Pereira, Ana M Martin, Sarah A Brough, Rachel McCarthy, Afshan Taylor, Jessica R Kim, Jung-Sik Waldman, Todd Lord, Christopher J Ashworth, Alan EMBO Mol Med Report 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. WILEY-VCH Verlag 2009-09 /pmc/articles/PMC3378149/ /pubmed/20049735 http://dx.doi.org/10.1002/emmm.200900041 Text en Copyright © 2009 EMBO Molecular Medicine
spellingShingle Report
Mendes-Pereira, Ana M
Martin, Sarah A
Brough, Rachel
McCarthy, Afshan
Taylor, Jessica R
Kim, Jung-Sik
Waldman, Todd
Lord, Christopher J
Ashworth, Alan
Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title_full Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title_fullStr Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title_full_unstemmed Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title_short Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors
title_sort synthetic lethal targeting of pten mutant cells with parp inhibitors
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3378149/
https://www.ncbi.nlm.nih.gov/pubmed/20049735
http://dx.doi.org/10.1002/emmm.200900041
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