Cancer: Drug with new approach on impeding DNA repair shows promise in
first clinical trial

Date:
June 15, 2020
Source:
Dana-Farber Cancer Institute
Summary:
Berzosertib, an ATR-targeting drug, improves progression-free
survival in combination with chemotherapy in patients with
high-grade serous ovarian cancer.



FULL STORY ==========================================================================
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.


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As detailed in a paper published online today by The Lancet Oncology,
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 findings may set the stage for testing
berzosertib -- an inhibitor of the ATR protein - - in a range of other
cancers, investigators say.

"Our results in his 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 Dana- Farber.

Berzosertib is designed to take advantage of one of the most glaring vulnerabilities of some cancer cells. Like a tractor run non-stop,
a tumor cell, driven by a constant imperative to proliferate, is apt
to need frequent repairs. In a tumor cell, that involves fixing broken
strands of DNA.

HGSOC, like other types of cancer, relies heavily on the ATR protein
in making those repairs. That reliance becomes even greater when these
cancers are treated with chemotherapy, which disrupts cells' ability to
copy their DNA.

"The unbridled growth of cancer cells places enormous stress on the
process of DNA replication," Konstantinopoulos explains. "ATR helps them survive that stress: its job is to coordinate the halting of the cell
cycle to check if the DNA is intact or needs repair. Drugs that inhibit
ATR -- that deprive tumor cells of such repair -- have the potential to be particularly effective in some cancers." In the study, investigators at
11 cancer centers around the country enrolled 70 patients with HGSOC that
was resistant to platinum-based chemotherapy. Half the participants were randomly assigned to receive the standard chemotherapy agent gemcitabine
alone and half received gemcitabine in combination with berzosertib.

The estimated median progression-free survival of patients receiving gemcitabine alone -- the period in which their disease was in retreat or
stable -- was 14.7 weeks. For those receiving gemcitabine and berzosertib,
it was 22.9 weeks. Among patients with the most platinum resistant tumors
(i.e. those who had progressed within 3 months from prior platinum-based chemotherapy), the difference was even greater: 9 weeks for gemcitabine
versus 27.7 weeks for gemcitabine and berzosertib.

Side effects were similar in the two groups. Those receiving the
combination therapy, however, had a higher rate of thrombocytopenia,
or low blood platelet levels.


========================================================================== Story Source: Materials provided by Dana-Farber_Cancer_Institute. Note:
Content may be edited for style and length.


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Link to news story: https://www.sciencedaily.com/releases/2020/06/200615184158.htm

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