The CHK1 Inhibitor Prexasertib Exhibits Monotherapy Activity in High-Grade Serous Ovarian Cancer Models and Sensitizes to PARP Inhibition
Abstract
PARP inhibitors are approved for the treatment of high-grade serous ovarian cancers (HGSOC). Therapeutic resistance, resulting from restoration of homologous recombination (HR) repair or replication fork stabilization, is a pressing clinical problem. We assessed the activity of prexasertib, a checkpoint kinase 1 (CHK1) inhibitor known to cause replication catastrophe, as monotherapy and in combination with the PARP inhibitor olaparib in preclinical models of HGSOC, including those with acquired PARP inhibitor resistance.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 15, 2019
- Source ID
- 10.1158/1078-0432.ccr-19-0448
Entities
People
- Alan D'Andrea
- Anniina Färkkilä
- Bose S. Kochupurakkal
- Chunyu Yang
- Connor E. Dunn
- Elizaveta Reznichenko
- Geoffrey I. Shapiro
- Hunter D. Reavis
- Jean-bernard Lazaro
- Joyce F. Liu
- Kalindi Parmar
- Khanh T. Do
- Larissa A. Sambel
- Lee Zou
- Panagiotis A Konstantinopoulos
- Paul T. Kirschmeier
- Sangeetha Palakurthi
- Ursula A. Matulonis
- Zhigang C. Wang
Organizations
- Dana–Farber Cancer Institute
- Harvard Medical School
- National Institutes of Health
- United States Department of Defense