Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer.

Gupta VG, Hirst J, Petersen S, Roby KF, Kusch M, Zhou H, Clive ML, Jewell A, Pathak HB, Godwin AK, Wilson AJ, Crispens MA, Cybulla E, Vindigni A, Fuh KC, Khabele D. Entinostat, a selective HDAC1/2 inhibitor, potentiates the effects of olaparib in homologous recombination proficient ovarian cancer. Gynecologic oncology. 2021 Dec;162(162). 163-172. PMID: 33867143 [PubMed] PMCID: PMC8647995 NIHMSID: NIHMS1749878.

Abstract

Poly ADP ribose polymerase inhibitors (PARPi) are most effective in BRCA1/2 mutated ovarian tumors. Better treatments are needed for homologous recombination HR-proficient cancer, including CCNE1 amplified subtypes. We have shown that histone deacetylase inhibitors (HDACi) sensitize HR-proficient ovarian cancer to PARPi. In this study, we provide complementary preclinical data for an investigator-initiated phase 1/2 clinical trial of the combination of olaparib and entinostat in recurrent, HR-proficient ovarian cancer.