Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Identifies Potential Therapeutic Target for Incurable, Rare Type of Soft-Tissue Cancer

Published: Friday, December 27, 2013
Last Updated: Thursday, December 26, 2013
Bookmark and Share
UT Southwestern scientists study published online in Cell Reports.

A deadly, rare type of soft-tissue cancer may be completely eradicated simply by inhibiting a key protein involved in its growth, UT Southwestern Medical Center researchers report.

In the study, published online in Cell Reports, scientists found that inhibiting the action of a protein called BRD4 caused cancer cells to die in a mouse model of malignant peripheral nerve sheath tumors (MPNSTs).

“This study identifies a potential new therapeutic target to combat MPNST, an incurable type of cancer that is typically fatal,” said Dr. Lu Le, Assistant Professor of Dermatology at UT Southwestern and senior author of the study. “The findings also provide important insight into what causes these tumors to develop.”

MPNSTs are highly aggressive sarcomas that form around nerves. These tumors can develop sporadically, but about half of cases are in patients with a genetic disorder called neurofibromatosis type 1 (NF1) that affects 1 in 3,500 people. About 10 percent of NF1 patients will develop MPNST, which usually evolves from a benign but often large and disfiguring tumor called a plexiform neurofibroma.

Up to now, the preferred treatment for MPNST has been surgical removal, but that oftentimes is difficult or impossible due to the tumor’s location around nerves. Radiation and chemotherapy are other options, but their effectiveness is limited. The five-year survival rate for MPNST patients is about 50 percent.

By studying changes in cells as they evolved into cancerous MPNSTs, researchers in Dr. Le’s laboratory were able to determine that BRD4, a bromodomain protein that binds to DNA to regulate gene activation, is expressed at an unusually high level in MPNST cancer cells.

This action caused another protein called BCL-2 to keep cancer cells from dying. Alternately, when researchers inhibited BRD4 either genetically in the mice or pharmacologically by administering a compound called JQ1, the tumors shrank.

“These treatments suppressed tumor growth and caused the cancer cells to undergo apoptosis, or cell death. This is why BRD4 inhibition is exquisitely effective against MPNSTs and may represent a paradigm shift in therapy for these patients,” Dr. Le said.

The same class of drug used in the experiments is currently being evaluated in phase 1 and 2 trials for treatment of leukemia and a subtype of lung cancer. Meanwhile, UT Southwestern is working with a pharmaceutical company to develop a similar BRD4-inhibiting drug to launch a clinical trial for MPNST patients.

New drugs are desperately needed to treat MPNST and provide hope to NF1 patients at highest risk for this cancer, said Dr. Le, who also serves as Co-director of UT Southwestern’s Comprehensive Neurofibromatosis Clinic. The clinic offers neurofibromatosis patients access to the latest clinical trials and treatments.

Co-directed by Dr. Laura Klesse, Assistant Professor of Pediatrics, the clinic is part of the Harold C. Simmons Comprehensive Cancer Center and serves patients with all three types of hereditary neurofibromatosis, including the dominant NF1 type and rarer NF2 and Schwannomatosis forms.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

HIV Protein Manipulates Hundreds of Human Genes
Findings search for new or improved treatments for patients with AIDS.
Thursday, January 28, 2016
Researchers Find a Small Protein that Plays a Big Role in Heart Muscle Contraction
New protein, DWORF, stimulates a calcium-ion pump that controls muscle contraction.
Friday, January 15, 2016
UTSW-led Study Establishes Biomarkers to Help Diagnose, Treat Psychosis
In this study, the Bipolar-Schizophrenia Network on Intermediate Phenotypes identified three neurobiologically distinct biotypes.
Saturday, December 12, 2015
Physiologists Uncover a New Code at the Heart of Biology
New “code” - the speed limit of assembly - dictate the ultimate function of a given protein.
Thursday, September 24, 2015
Cell that Replenishes Heart Muscle Found by UT Southwestern Researchers
Researchers devise a new cell-tracing technique to detect cells that do replenish themselves.
Tuesday, June 23, 2015
Researchers Find Molecular Mechanisms within Fetal Lungs that Initiate Labor
Biochemists found that steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2) proteins control genes.
Tuesday, June 23, 2015
MAGE Genes Provide Insight into Optimizing Chemotherapy
UT Southwestern Medical Center scientists have identified a new biomarker that could help identify patients who are more likely to respond to certain chemotherapies.
Tuesday, February 17, 2015
Researchers Find New Mechanism That Controls Immune Responses
The findings appear online in the journal Science.
Friday, February 13, 2015
Protein Variant may Boost Cardiovascular Risk by Hindering Blood Vessel Repair
Researchers have found that apoE3 helps repair the lining of blood vessels.
Friday, September 19, 2014
UTSW Cancer Researchers Identify Irreversible Inhibitor for KRAS Gene Mutation
Irreversible inhibitor for KRAS gene mutation involved in lung, colon, and pancreatic cancers.
Tuesday, July 29, 2014
UT Southwestern Researcher Selected for ASBMB Merck Award
Award recognizes Dr. Zhijian Chen’s outstanding contributions to research in biochemistry and molecular biology.
Friday, July 18, 2014
Cellular Force That Drives Allergy and Asthma Can be Blocked by Interferon
Type I interferons block the development of allergy- and asthma-driving Th2 cells.
Friday, June 20, 2014
Proteins Causing Daytime Sleepiness Also Tied to Bone Formation
Orexin proteins provide target for osteoporosis, UT Southwestern researchers find.
Saturday, June 14, 2014
New Mechanism Explains How Cancer Cells Spread
A protein critical to the spread of deadly cancer cells has been identified and how it works determined.
Wednesday, May 28, 2014
Stem Cell Study Opens Door to Undiscovered World of Biology
Discovery published in Nature measures protein production.
Tuesday, March 11, 2014
Scientific News
Structure of Brain Plaques in Huntington's
Researchers at the University of Pittsburgh School of Medicine have shown that the core of the protein clumps found in the brains of people with Huntington's disease have a distinctive structure, a finding that could shed light on the molecular mechanisms underlying the neurodegenerative disorder.
Visualizing a Cancer Drug Target at Atomic Resolution
Using cryo-electron microscopy, researchers were able to view, in atomic detail, the binding of a potential small molecule drug to a key protein in cancer cells.
Pumpjack" Mechanism for Splitting and Copying DNA
High-resolution structural details of cells' DNA-replicating proteins offer new insight into how these molecular machines function
The Power of Three
Overlooked portion of cell “death receptor” critical in some cancers, autoimmune diseases.
Biomarker for Recurring HPV-Linked Oropharyngeal Cancers
A look-back analysis of HPV infection antibodies in patients treated for oropharyngeal (mouth and throat) cancers linked to HPV infection suggests at least one of the antibodies could be useful in identifying those at risk for a recurrence of the cancer, say scientists at the Johns Hopkins University.
Light Signals from Living Cells
Fluorescent protein markers delivered under high pressure.
Cellular 'Relief Valve'
A team led by scientists at The Scripps Research Institute (TSRI) has solved a long-standing mystery in cell biology by showing essentially how a key “relief-valve” in cells does its job.
Genomic Signature Shared by Five Types of Cancer
National Institutes of Health researchers have identified a striking signature in tumor DNA that occurs in five different types of cancer.
Protein Protects Against Flu in Mice
The engineered molecule doesn’t provoke inflammation and may hail a new class of antivirals.
Cat Stem Cell Therapy Gives Humans Hope
By the time Bob the cat came to the UC Davis veterinary hospital, he had used up most of his nine lives.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!