Background Prostate cancer is a heterogeneous disease, but current treatments are not based
on molecular stratification. We hypothesized that metastatic, castration-resistant prostate …

There have been major advances in our understanding of the cellular and molecular biology
of the human malignancies that are collectively referred to as ovarian cancer. At a recent …

To identify approaches to target DNA repair vulnerabilities in cancer, we discovered
nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase …

Purpose: PARP1/2 inhibitors are a class of anticancer agents that target tumor-specific defects
in DNA repair. Here, we describe BMN 673, a novel, highly potent PARP1/2 inhibitor with …

BRCA1 and BRCA2 are important for DNA double-strand break repair by homologous
recombination 1 , and mutations in these genes predispose to breast and other cancers 2 . Poly(…

PARP inhibitors ( PARPi ) for the treatment of BRCA1 or BRCA2 deficient tumours are currently
the focus of seminal clinical trials exploiting the concept of synthetic lethality. Although …

Small-molecule inhibitors of PARP1/2, such as olaparib, have been proposed to serve as a
synthetic lethal therapy for cancers that harbor BRCA1 or BRCA2 mutations. Indeed, in …

PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the
first clinically approved drugs designed to exploit synthetic lethality, a genetic concept …

Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach
to the development of targeted cancer therapies. Mutations in ARID1A represent one of …

Genomic instability is one of the most pervasive characteristics of tumour cells and is probably
the combined effect of DNA damage, tumour-specific DNA repair defects, and a failure to …