Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Some patients with incurable tumors and BRCA mutations respond to new 2-drug combination

08.04.2013
A novel combination of two drugs has shown anti-cancer activity in patients who had incurable solid tumors and carried a germline mutation in their BRCA genes, Dana-Farber Cancer Institute researchers are reporting at the American Association for Cancer Research annual meeting in Washington, April 6-10.
The findings (abstract LB-202) will be released at a press conference on Sunday, April 7, 2 p.m. ET, and later at an oral presentation on Tuesday, April 9, 2 p.m. ET, in Room 153, in the Washington Convention Center.

The two oral drugs, sapacitabine and seliciclib, were given sequentially in a phase 1 clinical trial that is mainly enrolling patients whose tumors lack BRCA function because of an inherited mutation.

"We have seen several responses among these patients, as well as instances of prolonged stable disease lasting more than a year," said Geoffrey Shapiro, MD, PhD, director of Dana-Farber's Early Drug Development Center (EDDC). As a result, he said that a BRCA mutation may be a potential biomarker that identifies patients who are more likely to respond to the drug combination.

Sixteen patients enrolled in the trial carried an inherited BRCA mutation. Four of these patients had partial responses – a 30 percent or greater shrinkage of tumor mass – including one with pancreatic, two with breast, and one with ovarian cancer. Three patients were continuing to have a partial response at the time of presentation of the data, with the longest lasting more than 78 weeks. Two additional BRCA mutation carriers, with breast and ovarian cancer, experienced stable disease for 21 and 64 weeks, respectively. Of the remaining 22 patients enrolled in the trial, six experienced stable disease for 12 weeks or more.

Sapacitabine is toxic to cancer cells by causing damage to their DNA, which, if not repaired, causes the cells to self-destruct. The BRCA protein is essential for repair of the DNA damage caused by sapacitabine, so patients with mutations that inactivate BRCA may be more sensitive to the drug's activity.

The second drug, seliciclib, is an inhibitor of cyclin-dependent kinases (CDKs), enzymes that have multiple cellular functions, including a role in DNA repair, further augmenting the effects of sapacitabine. The patients in the trial received sapacitabine twice daily for seven days, followed by seliciclib twice daily for three days. Adverse events were mild to moderate in intensity, the study found.

Shapiro and colleagues are continuing to enroll BRCA mutation carriers in the trial, and hope to determine if the mutations may serve as a biomarker for response. He said that these drugs may prove to be an important treatment alternative for patients with BRCA-deficient cancers.

This research was supported in part by Cyclacel Ltd., and the National Institutes of Health (RO1 CA90687).

--Written by Richard Saltus, Dana-Farber Cancer Institute

About Dana-Farber Cancer Institute

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute. It provides adult cancer care with Brigham and Women's Hospital as Dana-Farber/Brigham and Women's Cancer Center and it provides pediatric care with Boston Children's Hospital as Dana-Farber/Children's Hospital Cancer Center. Dana-Farber is the top ranked cancer center in New England, according to U.S. News & World Report, and one of the largest recipients among independent hospitals of National Cancer Institute and National Institutes of Health grant funding. Follow Dana-Farber on Facebook: http://www.facebook.com/danafarbercancerinstitute and on Twitter: @danafarber.

Teresa Herbert | EurekAlert!
Further information:
http://www.dfci.harvard.edu

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>