Navigation Links
Biomarker may identify neuroblastomas with sensitivity to BET bromodomain inhibitors
Date:2/21/2013

PHILADELPHIA Neuroblastoma, the most common malignant tumor of early childhood, is frequently associated with the presence of MYCN amplification, a genetic biomarker associated with poor prognosis. Researchers have determined that tumors containing MYCN amplification are sensitive to a new class of drugs, BET bromodomain inhibitors.

The researchers made this discovery in a preclinical study, which was funded in part by a Stand Up To Cancer Innovative Research Grant and was published in Cancer Discovery, a journal of the American Association for Cancer Research.

"BET bromodomain inhibitors are a class of drugs that many researchers are hopeful may offer a new therapeutic option for treating patients with certain cancers," said Kimberly Stegmaier, M.D., assistant professor of pediatrics in the Department of Hematology/Oncology at Dana-Farber/Children's Hospital Cancer Center in Boston, Mass. "The challenge has been identifying biomarkers that can help direct clinical translation of these drugs by pinpointing those patients with the highest likelihood of response."

To identify genetic biomarkers of responsiveness to BET bromodomain inhibitors, Stegmaier and colleagues screened more than 600 cancer cell lines with known genetic characteristics for sensitivity to a prototypical BET bromodomain inhibitor.

Using this high-throughput, cell-based screening process, the researchers found that neuroblastoma cells in which the MYCN gene was amplified were sensitive to BET bromodomain inhibitors.

"Neuroblastoma is a devastating childhood cancer, and only a minority of children with high-risk disease will be cured with currently available treatments," Stegmaier said. "Prior research has shown that MYCN amplification is common in neuroblastoma, but it has been an elusive drug target."

To further validate their findings, the researchers tested a BET bromodomain inhibitor, from the laboratory of James E. Bradner, M.D., at the Dana-Farber Cancer Institute, using cultured MYCN-amplified neuroblastoma cell lines and three animal models of MYCN-amplified neuroblastoma. Together, they found that the drug decreased levels of MYCN protein in cultured cells, and that this led to impaired cell growth and cell death. In each animal model, including a mouse model of neuroblastoma that is known to be resistant to many standard therapies, the drug was shown to have anti-tumor effects and to prolong survival.

"My Stand Up To Cancer grant, which focused on modulating difficult drug targets in childhood cancers, was instrumental to us being able to do this exciting work," Stegmaier said. "These types of studies are generally considered high-risk, particularly because they start with unbiased screening, and they are generally less likely to be supported by traditional sources of funding."


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. SomaLogic publishes proteomic biomarker analysis of lung cancer tissue samples
2. Biomarkers can reveal IBS
3. Mayo Clinic researchers discover biomarkers for prostate cancer detection, recurrence
4. Early biomarker for pancreatic cancer identified
5. New biomarker test predicts arthritis at much earlier stage, MU researchers say
6. Biomarker predicts response to cancer treatment
7. Novel biomarkers reveal evidence of radiation exposure
8. GW researchers discover biomarker for advanced bile duct fibrosis and bile duct cancer
9. Using biomarkers to identify and treat schizophrenia
10. US Army: Pre-injury cartilage biomarkers associated with subsequent ACL injuries
11. Biomarkers of behavior, therapeutic targets for adult B-acute lymphoblastic leukemia identified
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/1/2016)... ... ... 2 is a set of versatile and smooth logo reveals built exclusively for Final ... a unique logo reveal in just a matter of minutes. Custom settings give the user ... add a uniquely animated logo to any photos or videos. , ProBrand Reveal comes packaged ...
(Date:4/30/2016)... ... 30, 2016 , ... Create an abstract shape animation with ... manipulate three-dimensional shapes with ease all within Apple Motion . Users have ... texture animation, opacity texture animation, overall shape texture displacement, twist, camera controls, and ...
(Date:4/30/2016)... ... April 30, 2016 , ... Dr. Trevor Gardner, President ... today signed a multifaceted agreement which will allow for the research and development ... of Natural and Applied Sciences, Allied Health and Nursing will work together to ...
(Date:4/29/2016)... ... April 30, 2016 , ... World ... the Pick Up Springboard, an automotive invention that improves the storage features of ... worth $162 billion," says Scott Cooper, CEO and Creative Director of World Patent ...
(Date:4/29/2016)... ... April 29, 2016 , ... Memorial Healthcare System ... Medical Education (ACGME) that it has received accreditation for its residency program on ... residency programs that Memorial is currently pursuing, including Pediatrics and Internal Medicine. This ...
Breaking Medicine News(10 mins):
(Date:4/27/2016)... , April 27, 2016 ... announced the launch of a Phase 2 clinical study ... hearing in patients undergoing cochlear implantation (CI) surgery. This ... patients in Germany and ... the middle ear at the time of surgery. "Despite ...
(Date:4/26/2016)... CHICAGO , April 26, 2016 Hill-Rom Holdings, ... to a management presentation at the Deutsche Bank 41 st ... at 2:50 p.m. EDT. You are invited to ... http://ir.hill-rom.com/events.cfm or access it directly at http://edge.media-server.com/m/p/mr4uxgas ... one hour after conclusion of the live event and accessible ...
(Date:4/26/2016)... , April 27, 2016 Research ... "Global Molecular Diagnostics Market 2016-2020" report to their ... , ,The global molecular diagnostics market is projected to ... 2016-2020. Molecular diagnostics is a technique that ... the molecular level to detect changes in biochemical pathways. ...
Breaking Medicine Technology: