Open AccessSynthetic lethal targeting of PTEN mutant cells with PARP inhibitors
Author(s) -
MendesPereira Ana M.,
Martin Sarah A.,
Brough Rachel,
McCarthy Afshan,
Taylor Jessica R.,
Kim JungSik,
Waldman Todd,
Lord Christopher J.,
Ashworth Alan
Publication year - 2009
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.200900041
Subject(s) - pten , tensin , synthetic lethality , cancer research , poly adp ribose polymerase , biology , parp inhibitor , dna repair , tumor suppressor gene , homologous recombination , mutant , genome instability , olaparib , mutation , suppressor , dna damage , gene , polymerase , genetics , dna , pi3k/akt/mtor pathway , carcinogenesis , apoptosis
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.