Drug (Berzosertib) That Inhibits DNA Repair Shows Promise in First Clinical Trial, When Combined with Standard Chemotherapy, in Ovarian Cancer

In its first randomized clinical trial, a drug that targets a protein needed by cancer cells to maintain their dogged growth and division has shown considerable promise in combination with chemotherapy in patients with a common form of ovarian cancer, investigators at Dana-Farber Cancer Institute report. As detailed in a paper published online on June 15, 2020 in The Lancet Oncology (https://www.sciencedirect.com/science/article/abs/pii/S1470204520301807), patients with high-grade serous ovarian cancer (HGSOC) who were treated with the drug, berzosertib, and chemotherapy lived substantially longer before their disease began to worsen than did those treated with chemotherapy alone. The article is titled “Berzosertib Plus Gemcitabine Versus Gemcitabine Alone in Platinum-Resistant High-Grade Serous Ovarian Cancer: A Multicentre, Open-Label, Randomised, Phase 2 Trial.” The findings may set the stage for testing berzosertib--an inhibitor of the ATR protein--in a range of other cancers, investigators say. [Editor’s Note: ATR is a serine/threonine protein kinase that is also known as ataxia telangiectasia and Rad3-related protein; it is involved in sensing DNA damage and activating the DNA damage checkpoint, leading to cell cycle arrest.] "Our results in this phase 2 trial suggest that ATR inhibition in combination with chemotherapy has the potential to offer significant benefit to patients with chemotherapy-resistant HGSOC and, potentially, other tumor types where ATR plays a key role," says the study's lead author, Panagiotis Konstantinopoulos, MD, PhD, Director of Translational Research, Gynecologic Oncology, at the Dana-Farber Cancer Institute (DFCI). Berzosertib is designed to take advantage of one of the most glaring vulnerabilities of some cancer cells.
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