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

New Insights into Neuroblastoma Tumor Suppressor may Provide Clues for Improved Treatment

Published: Thursday, August 15, 2013
Last Updated: Thursday, August 15, 2013
Bookmark and Share
Loss of a gene required for stem cells in the brain to turn into neurons may underlie the most severe forms of neuroblastoma, a deadly childhood cancer of the nervous system.

Published in Developmental Cell today, the findings also provide clues about how to improve treatment of this often-incurable tumor.

Neuroblastoma can appear in nervous tissue in the abdomen, chest and spine, among other regions of the body, and can spawn body-wracking metastasis. The most severe tumors respond poorly to treatment and the disease accounts for 15 percent of cancer deaths in children.

Johan Holmberg, PhD, at the Ludwig Institute for Cancer Research Stockholm took a close look at the role of the CHD5 tumor suppressor during normal nervous system development. Previous studies had shown that the gene CHD5 is often inactivated in the most severe forms of neuroblastoma, but little was known about its function in healthy tissue or how it operates. The study, which was conducted in close collaboration with colleagues at Trinity College, Dublin, Ireland, addressed these two key issues.

The researchers found that CHD5 is required for the cellular transition from a stem cell to a mature neuron. In one experiment, the researchers knocked down the CHD5 gene by injecting a small RNA into the brains of fetal mice while in the womb.

"The result was a complete absence of neurons," says Ludwig researcher Holmberg who is based at the Karolinska Institutet. “Instead of becoming neurons, the cells with CHD5 knocked down stayed in a limbo-like state between an actively-dividing stem cell and a mature nerve cell. It was a very robust effect," added Holmberg.

The researchers also dissected how CHD5 operates, showing that it sticks to certain modifications of histone proteins. These modifications help control how genes are turned on and off. In the absence of CHD5, key stem cell genes are not turned off, and genes required for neuronal maturation are not turned on. The findings highlight how the failure of a cell to properly mature into its terminal state can underlie cancer, a relatively understudied area of research.

"It is necessary for cells in the healthy nervous tissue to be able to go from stem cells to neurons," explains Holmberg. "If you lose this capacity, these cells become locked in an immature state, which might yield quite dangerous tumor cells, especially in combination with additional cancer-promoting cellular events.”

The research could also lead to new ways to treat neuroblastoma, perhaps using currently approved drugs. One component of neuroblastoma treatment is retinoic acid, a drug that can drive neuronal maturation. Holmberg and his colleagues found that knocking down the expression of CHD5 in more benign neuroblastoma cells blocked their capacity to mature in response to retinoic acid treatment. "These cells were completely insensitive to treatment, no matter how much we gave them, mirroring the same unresponsiveness to retinoic acid in the more malignant CHD5-negative neuroblastoma cells,” says Holmberg.

The results of these cell-based experiments are consistent with clinical findings that retinoic acid is often unsuccessful in patients with severe forms of the disease. Holmberg reasons that if CHD5 could be re-activated in such hard-to-treat patients, it might increase responsiveness to retinoic acid. The findings may also have relevance for other types of tumors. For instance, CHD5 is often inactivated in glioblastoma multiforme, the most common and most aggressive form of brain cancer in adults.

Funding for this research came in part from Science Foundation Ireland; the Health Research Board; the Swedish Cancer Society, the Swedish Research Council, the Lilian Sagen and Curt Eriksson Research Foundation; DBRM; the Swedish Childhood Cancer Foundation; the Danish National Research Foundation; the Lundbeck Foundation; and the Novo Nordisk Foundation.

Holmberg is the head of the head of the CNS Tumors and Development lab at the Ludwig Institute for Cancer Research Stockholm where he is based at the Karolinska Institutet.


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 3,300+ scientific posters on ePosters
  • More than 4,900+ 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.


Scientific News
Liquid Biopsies: Miracle Diagnostic or Next New Fad?
Thanks to the development of highly specific gene-amplification and sequencing technologies liquid biopsies access more biomarkers relevant to more cancers than ever before.
Triple-Action Therapy Patch Shows Promise
Patch that delivers drug, gene, and light-based therapy to tumor sites shows promising results in mice.
Cancer Gene-Drug Combinations Ripe for Precision Medicine
The study aims to expand the number of cancer gene mutations that can be paired with a precision therapy.
Exploiting Malaria’s Achilles’ Heel
Researchers have uncovered an Achilles' heel in malaria's anti-drug treatment arsenal that could lead to a disease cure.
Targeting BRAF Mutations in Thyroid Cancer
Treating metastatic thyroid cancer patients harboring a BRAF mutation with vemurafenib showed anti-tumor activity in a third of patients.
Colon Cancer Blocked in Mice
Case Western Reserve University Researchers block common type of colon cancer tumour in mice, laying groundwork for human clinical trial.
Protein Nanocages Could Improve Drug Design and Delivery
HHMI scientists have designed and built 10 large protein icosahedra that are similar to viral capsids that carry viral DNA.
Cancer Related Immune Response Genes Uncovered
Researchers at the SBP have identified over 100 new genetic regions that affect the immune response to cancer.
New Therapeutic Targets For Small Cell Lung Cancer Identified
Researchers at UTSW Medical Center have identified a protein termed ASCL1 that is essential to the development of small cell lung cancer.
Liquid Biopsies Treating Ovarian Cancer
Researchers have discovered a promising monitor and treat recurrence of ovarian cancer. Detecting cancer long before tumours reappear.
SELECTBIO

SELECTBIO Market Reports
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
3,300+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,900+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!