Novel Small Molecule Inhibitor for Treatment of PARP inhibitor-Resistant Ovarian Cancer

PARP inhibitors (PARPi) are FDA-approved targeted drugs for ovarian and breast cancers with BRCA mutations or homologous recombination (HR) repair deficiency.
However, at least 50% of ovarian cancer has no HR deficiency and is resistant to PARPi therapy. Furthermore, PARPi-sensitive cancers can potentially restore HR repair and develop resistance to PARPi in patients.
Dr. Elena Ratner’s lab at Yale performed in silico screening and discovered a novel small molecule inhibitor DB4 that blocks HR repair and renders PARPi-resistant cancer cells hypersensitive to PARPi, such as olaparib and niraparib.
Combination of DB4 and olaparib efficaciously suppresses the progression of PARPi-resistant ovarian cancer xenografts and significantly prolongs the survival time of mice.
Intellectual Property: Patent application pending
Reference: Lin et al., Sci Rep. 2021 Apr 13;11(1):8042.