Navigation Links
Benefit of novel drug in breast cancer seen in blood within weeks

SAN FRANCISCO Clinical benefit from use of a novel histone deacetylase inhibitor drug may be determined by examining blood cells days after a patient receives treatment. The drug, entinostat, is the first histone deacetylase inhibitor successfully tested in a randomized, placebo-controlled study in metastatic breast cancer and is the first to show that clinical outcome can be predicted shortly after administration.

The findings, reported at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011, represent an advance in the goal to offer patients only those therapies that will help treat cancer effectively, the researchers said.

"The ability to have a marker of benefit within the first several weeks of using this drug represents an exciting advance in personalized medicine," said lead researcher Peter Ordentlich, Ph.D., executive director of translational science and a founder of Syndax Pharmaceuticals Inc. in Waltham, Mass. Syndax Pharmaceuticals developed entinostat, an oral small-molecule drug that inhibits enzymes that alter the packaging of DNA inside the nucleus, which controls gene expression.

"The goal of entinostat in breast cancer is to extend the benefit of hormone therapy and delay the time that patients will need to use chemotherapy," said Ordentlich. More than 160,000 women are diagnosed each year with estrogen receptor (ER)-positive invasive breast cancer, and many are treated with agents that block the hormone. But most women become resistant to these therapies, and entinostat, combined with antihormone agents, is meant to extend their benefit, he said.

To test that strategy in ER-positive metastatic breast cancer, Syndax Pharmaceuticals conducted ENCORE-301, a randomized, placebo-controlled, phase 2 study (n=130) testing the use of exemestane, an aromatase inhibitor, with either entinostat or placebo.

Results of the clinical trial, released in September, showed that the combination therapy delayed cancer progression by 27 percent (4.3 vs. 2.3 months) compared with exemestane treatment alone. At a median follow-up of 18 months, overall survival was also significantly longer with exemestane plus entinostat than with exemestane plus placebo (26.9 vs. 20.3 months).

In this subset analysis, researchers examined blood samples from 49 patients (27 received combination therapy) to evaluate whether changes in circulating blood cells that reflected the activity of the histone deacetylase (HDAC) inhibitor could be detected. Researchers measured protein lysine acetylation, a biological marker of entinostat activity, in B cells, T cells and monocytes in blood samples taken at pretreatment and one, eight and 15 days after therapy with entinostat, which is taken once a week.

While levels of lysine acetylation after one day were not linked to clinical benefit, levels measured eight and 15 days after therapy were related to clinical benefit, Ordentlich said. Researchers found that patients with elevated levels of protein lysine acetylation had a 68 percent reduced risk for disease progression compared with those patients who did not have sustained elevated levels.

Researchers found that hyperacetylation was also associated with longer median progression-free survival across cell lines: B cells, 8.5 vs. 1.9 months; T cells, 6.6 vs. 1.8 months; and monocytes, 6.2 vs. 1.9 months. "Those patients who were able to maintain acetylation did well," Ordentlich said.

He added that entinostat's long half-life and unique pharmacology allow researchers to quickly gauge the agent's activity. In this way, "we gain insight into how to use HDAC inhibitors, as a class of cancer drugs, in a variety of solid tumors," he said.


Contact: Jeremy Moore
American Association for Cancer Research

Related biology news :

1. Advanced Medical Care for At-Risk Newborns Nets Economic Benefits
2. Report provides new analysis of carbon accounting, biomass use, and climate benefits
3. Awareness and labeling initiatives can benefit inland fisheries
4. Obese adolescents benefit from high-dose vitamin D supplements
5. Vitamin D study suggests no mortality benefit for older women
6. Fatty acids involved in python heart growth could benefit diseased human heart
7. Turning slash piles into soil benefit
8. Commercial dry petfood has significant benefits for oral health in cats and dogs
9. Health benefits of broccoli require the whole food, not supplements
10. Everest expedition suggests nitric oxide benefits for intensive care patients
11. New study of Glovers Reef challenges whether corals will benefit from Marine Reserves protection
Post Your Comments:
(Date:5/24/2016)... Calif. , May 24, 2016 Ampronix facilitates superior patient care by ... LMD3251MT  3D medical LCD display is the latest premium product recently added to the ... ... ... Sony 3d Imaging- LCD Medical Display- Ampronix News ...
(Date:5/16/2016)... YORK , May 16, 2016   EyeLock ... solutions, today announced the opening of an IoT Center ... to strengthen and expand the development of embedded iris ... an unprecedented level of convenience and security with unmatched ... authenticate one,s identity aside from DNA. EyeLock,s platform uses ...
(Date:5/9/2016)... , UAE, May 9, 2016 ... when it comes to expanding freedom for high net ... Even in today,s globally connected world, there is ... conferencing system could ever duplicate sealing your deal with ... obtaining second passports by taking advantage of citizenship via ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , ... June 23, 2016 , ... ... pleased to announce the launch of their brand, UP4™ Probiotics, into Target stores ... 35 years, is proud to add Target to its list of well-respected retailers. ...
(Date:6/23/2016)... -- Houston Methodist Willowbrook Hospital has signed a ... serve as their official health care provider. As ... provide sponsorship support, athletic training services, and most ... athletes and families. "We are excited ... to bring Houston Methodist quality services and programs ...
(Date:6/23/2016)... FRANCISCO , June 23, 2016   EpiBiome ... has secured $1 million in debt financing from Silicon ... ramp up automation and to advance its drug development ... its new facility. "SVB has been an ... beyond the services a traditional bank would provide," said ...
(Date:6/23/2016)... 2016 Apellis Pharmaceuticals, Inc. today announced ... of its complement C3 inhibitor, APL-2. The trials ... dose studies designed to assess the safety, tolerability, ... in healthy adult volunteers. Forty subjects ... single dose (ranging from 45 to 1,440mg) or ...
Breaking Biology Technology: