PARP-1 inhibitor monotherapy and combination therapy in a preclinical mouse model of Brca2 mutant breast cancer

Hay, Trevor; Matthews, James R.; Pietzka, Lucie; Lau, Alan; Cranston, Aaron; Boulter, Robert; Nygren, Anders O.H.; Douglas-Jones, A.; Smith, Graeme C.M.; Martin, Niall M.B.; O’Connor, Mark J.; Clarke, Alan R.

doi:10.1186/bcr1979

Cited by 1 publication

(1 citation statement)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, PARPi exert direct DNA toxicity by trapping PARP1 (and PARP2) at damaged DNA where the PARP-DNA complexes are more cytotoxic than unrepaired single-strand DNA breaks themselves (Murai et al 2012). These preclinical results have been confirmed in vivo, where BRCA2-deficient tumors showed hypersensitivity to PARPi therapy with significant tumor regression (Hay et al 2009). …”

Section: Development Of Parp Inhibitors For Patients With Brca2-assocsupporting

confidence: 64%

Pancreatic ductal adenocarcinoma in BRCA2 mutation carriers

Mestier

Danset

Neuzillet

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

Germline BRCA2 mutations are the first known cause of inherited (familial) pancreatic ductal adenocarcinoma (PDAC). This tumor is the third most frequent cancer in carriers of germline BRCA2 mutations, as it occurs in around 10% of BRCA2 families. PDAC is known as one of the most highly lethal cancers, mainly because of its chemoresistance and frequently late diagnosis. Based on recent developments in molecular biology, a subgroup of BRCA2-associated PDAC has been created, allowing screening, early surgical treatment and personalized systemic treatment. BRCA2 germline mutation carriers who have ≥1 first-degree relative, or ≥2 blood relatives with PDAC, should undergo screening and regular follow-up based on magnetic resonance imaging and endoscopic ultrasound. The goal of screening is to detect early invasive PDAC and advanced precancerous lesions suitable for a stepwise surgical complete (R0) resection. Increasing evidence on the molecular role of the BRCA2 protein in the homologous recombination of DNA damages suggest that BRCA2-related PDAC are sensitive to agents causing DNA cross-linking damage, such as platinum salts, and treatments targeting rescue DNA repair pathways, such as poly(ADP-ribose) polymerase inhibitors that are currently under investigation.

show abstract

Section: Development Of Parp Inhibitors For Patients With Brca2-assocsupporting

confidence: 64%