2012
DOI: 10.1158/2159-8290.cd-12-0433
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The Promise of Combining Inhibition of PI3K and PARP as Cancer Therapy

Abstract: Summary: Analyses of in vitro and patient-derived in vivo models of breast cancer reveal that a combination of inhibitors of the enzymes PARP and phosphoinositide 3-kinase (PI3K) is a potentially effective treatment regimen for breast cancer tumors with elevated activity of the PI3K pathway. Cancer Discov; 2(11);

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Cited by 43 publications
(29 citation statements)
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“…PARP inhibitors have shown clinically significant activity in BRCA1 - or BRCA2 -mutated ovarian cancers (later-stage studies in BRCA -deficient TNBC patients are ongoing), due to a synthetic lethal mechanism in cells deficient in homologous combination-mediated DNA repair (Lord and Ashworth, 2016). Combinations of PI3K/mTOR pathway inhibitors and PARP inhibitors have also shown promising activity in prostate, ovarian and SCLC models (Cardnell et al, 2013; González-Billalabeitia et al, 2014; Rehman et al, 2012; Wang et al, 2016). Once again, results from an early clinical trial with buparlisib and olaparib suggest that toxicity will be a formidable obstacle to attaining the drug exposures needed to achieve an optimal therapeutic effect with this drug combination (Matulonis et al, 2016).…”
Section: Therapeutic Targeting Of the Pi3k Pathway In Cancermentioning
confidence: 99%
“…PARP inhibitors have shown clinically significant activity in BRCA1 - or BRCA2 -mutated ovarian cancers (later-stage studies in BRCA -deficient TNBC patients are ongoing), due to a synthetic lethal mechanism in cells deficient in homologous combination-mediated DNA repair (Lord and Ashworth, 2016). Combinations of PI3K/mTOR pathway inhibitors and PARP inhibitors have also shown promising activity in prostate, ovarian and SCLC models (Cardnell et al, 2013; González-Billalabeitia et al, 2014; Rehman et al, 2012; Wang et al, 2016). Once again, results from an early clinical trial with buparlisib and olaparib suggest that toxicity will be a formidable obstacle to attaining the drug exposures needed to achieve an optimal therapeutic effect with this drug combination (Matulonis et al, 2016).…”
Section: Therapeutic Targeting Of the Pi3k Pathway In Cancermentioning
confidence: 99%
“…However, neoadjuvant chemotherapy has much less impact in luminal breast cancers, and it has almost no activity in the luminal A subtype [4]. Finally, clinical benefit from HER2-targeting agents is largely restricted to women with HER2-enriched cancers, and there is the sense that inhibitors of poly(ADP-ribose) polymerase (PARP), which are very active in ovarian cancers that contain inactivating BRCA1 or BRCA2 mutations, may also be active in basal-like breast cancers, particularly if they are combined with other targeted agents [13].…”
Section: Key Pointsmentioning
confidence: 99%
“…Indeed, some promising combination treatments with PI3K inhibitors have recently been reported, such as with inhibitors of PARP (reviewed in Ref. [67]) or CDK4/6 (Ref. [68]) in breast cancer.…”
Section: Resultsmentioning
confidence: 99%