Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Study Reveals Genes That Drive Brain Cancer

Published: Tuesday, August 06, 2013
Last Updated: Tuesday, August 06, 2013
Bookmark and Share
About 15 percent of glioblastoma patients could receive personalized treatment with drugs currently used in other cancers.

A team of researchers at the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center has identified 18 new genes responsible for driving glioblastoma multiforme, the most common—and most aggressive—form of brain cancer in adults. The study was published August 5, 2013, in Nature Genetics.

“Cancers rely on driver genes to remain cancers, and driver genes are the best targets for therapy,” said Antonio Iavarone, MD, professor of pathology and neurology at Columbia University Medical Center and a principal author of the study.

“Once you know the driver in a particular tumor and you hit it, the cancer collapses. We think our study has identified the vast majority of drivers in glioblastoma, and therefore a list of the most important targets for glioblastoma drug development and the basis for personalized treatment of brain cancer.”

Personalized treatment could be a reality soon for about 15 percent of glioblastoma patients, said Anna Lasorella, MD, associate professor of pediatrics and of pathology & cell biology at CUMC.

“This study—together with our study from last year, Research May Lead to New Treatment for Type of Brain Cancer—shows that about 15 percent of glioblastomas are driven by genes that could be targeted with currently available FDA-approved drugs,” she said. “There is no reason why these patients couldn’t receive these drugs now in clinical trials.”

New Bioinformatics Technique Distinguishes Driver Genes from Other Mutations

In any single tumor, hundreds of genes may be mutated, but distinguishing the mutations that drive cancer from mutations that have no effect has been a longstanding problem for researchers.

The Columbia team used a combination of high throughput DNA sequencing and a new method of statistical analysis to generate a short list of driver candidates. The massive study of nearly 140 brain tumors sequenced the DNA and RNA of every gene in the tumors to identify all the mutations in each tumor. A statistical algorithm designed by co-author Raul Rabadan, PhD, assistant professor of biomedical informatics and systems biology, was then used to identify the mutations most likely to be driver mutations. The algorithm differs from other techniques to distinguish drivers from other mutations in that it considers not only how often the gene is mutated in different tumors, but also the manner in which it is mutated.

“If one copy of the gene in a tumor is mutated at a single point and the second copy is mutated in a different way, there’s a higher probability that the gene is a driver,” Dr. Iavarone said.

The analysis identified 15 driver genes that had been previously identified in other studies—confirming the accuracy of the technique—and 18 new driver genes that had never been implicated in glioblastoma.

Significantly, some of the most important candidates among the 18 new genes, such as LZTR1 and delta catenin, were confirmed to be driver genes in laboratory studies involving cancer stem cells taken from human tumors and examined in culture, as well as after they had been implanted into mice.
 
A New Model for Personalized Cancer Treatment

Because patients’ tumors are powered by different driver genes, the researchers say that a complicated analysis will be needed for personalized glioblastoma treatment to become a reality. First, all the genes in a patient’s tumor must be sequenced and analyzed to identify its driver gene.

“In some tumors it’s obvious what the driver is; but in others, it’s harder to figure out,” said Dr.Iavarone.

Once the candidate driver is identified, it must be confirmed in laboratory tests with cancer stem cells isolated from the patient’s tumor.

About 15 percent of glioblastoma driver genes can be targeted with currently available drugs, suggesting that personalized treatment for some patients may be possible in the near future. Personalized therapy for glioblastoma patients could be achieved by isolating the most aggressive cells from the patient’s tumor and identifying the driver gene responsible for the tumor’s growth (different tumors will be driven by different genes). Drugs can then be tested on the isolated cells to find the most promising candidate. In this image, the gene mutation driving the malignant tumor has been replaced with the normal gene, transforming malignant cells back into normal brain cells. Image: Anna Lasorella.

“Cancer stem cells are the tumor’s most aggressive cells and the critical cellular targets for cancer therapies,” said Dr. Lasorella. “Drugs that prove successful in hitting driver genes in cancer stem cells and slowing cancer growth in cell culture and animal models would then be tried in the patient.”
 
Personalized Treatment Already Possible for Some Patients

For 85 percent of the known glioblastoma drivers, no drugs that target them have yet been approved.

But the Columbia team has found that about 15 percent of patients whose tumors are driven by certain gene fusions, FDA-approved drugs that target those drivers are available.

The study found that half of these patients have tumors driven by a fusion between the gene EGFR and one of several other genes. The fusion makes EGFR—a growth factor already implicated in cancer—hyperactive; hyperactive EGFR drives tumor growth in these glioblastomas.

“When this gene fusion is present, tumors become addicted to it—they can’t live without it,” Dr. Iavarone said. “We think patients with this fusion might benefit from EGFR inhibitors that are already on the market. In our study, when we gave the inhibitors to mice with these human glioblastomas, tumor growth was strongly inhibited.”

Other patients have tumors that harbor a fusion of the genes FGFR (fibroblast growth factor receptor) and TACC (transforming acidic coiled-coil), first reported by the Columbia team last year. These patients may benefit from FGFR kinase inhibitors. Preliminary trials of these drugs (for treatment of other forms of cancer) have shown that they have a good safety profile, which should accelerate testing in patients with glioblastoma.


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 3,000+ scientific posters on ePosters
  • More Than 4,500+ 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

New Neurodevelopmental Syndrome Identified
Study pinpoints underlying genetic mutations, raising hopes for targeted therapies.
Friday, April 22, 2016
Major Complication of Parkinson’s Therapy Explained
Researchers have discovered why long-term use of ¬¬¬L-DOPA (levodopa), the most effective treatment for Parkinson’s disease, commonly leads to a movement problem called dyskinesia, a side effect that can be as debilitating as Parkinson’s disease itself.
Monday, September 14, 2015
An Innovative Algorithm to Decipher How Drugs Work Inside the Body
Researchers at Columbia University Medical Center (CUMC) have developed a computer algorithm that is helping scientists see how drugs produce pharmacological effects inside the body.
Friday, July 24, 2015
Neurons Controlling Appetite Made from Skin Cells
Cells provide individualized model for studying obesity and testing treatments.
Monday, March 02, 2015
Bone Stem Cells Shown To Regenerate Bone And Cartilage In Adult Mice
Cells could be exploited to treat osteoarthritis and osteoporosis.
Monday, January 19, 2015
Non-Gluten Proteins as Targets of Immune Response to Wheat in Celiac Disease
The results were reported online in the Journal of Proteome Research.
Thursday, December 18, 2014
Human Stem Cells Converted to Functional Lung Cells
Possibility of generating lung tissue for transplant using a patient’s own cells.
Thursday, December 05, 2013
New Link Between Obesity and Diabetes Found
Targeting a single enzyme that raises both sugar and insulin levels in the obese could prevent and treat diabetes.
Monday, November 25, 2013
Human Stem Cells Elucidate Mechanisms of Beta-Cell Failure in Diabetes
Mechanisms that impair insulin production in diabetes identified using a human stem cell model of Wolfram syndrome, a rare form of diabetes.
Thursday, November 14, 2013
Researchers Discover Cells that Restore Bladder’s Unique Lining
Finding that could lead to new ways to treat chronic bladder pain or to produce new tissue for patients with damaged bladders.
Tuesday, September 24, 2013
Trial Aims to Advance Prenatal Diagnosis of Genetic Defects
High-risk pregnant women being recruited for research on chromosomal abnormalities and incidence of birth defects, developmental delays.
Thursday, August 22, 2013
Is There a Role for Vitamins in Cancer Prevention?
According to recent national surveys, approximately 40 percent of U.S. adults take multivitamins/multiminerals.
Monday, August 12, 2013
DNA Robots Find and Tag Blood Cells
Researchers have created a fleet of molecular “robots” that can home in on specific human cells and mark them for drug therapy or destruction.
Thursday, August 08, 2013
Key Molecular Pathways Leading to Alzheimer’s Identified
Research approach highlights potential therapeutic targets.
Thursday, July 25, 2013
New Genetic Cause of Pulmonary Hypertension Identified
Study finds druggable target for rare fatal lung disease.
Thursday, July 25, 2013
Scientific News
How Skeletal Stem Cells Form The Blueprint Of The Face
USC researchers discover that two types of molecular signals work to control where and when stem cells turn into facial cartilage.
Ketamine Metabolism Lifts Depression
NIH-funded team finds rapid-acting, non-addicting agent in mouse study.
Faster, Cheaper Way to Produce New Antibiotics
A novel way of synthesising a promising new antibiotic has been identified by scientists at the University of Bristol.
Process Contaminants in Vegetable Oils and Foods
Glycerol-based process contaminants found in palm oil, but also in other vegetable oils, margarines and some processed foods, raise potential health concerns for average consumers of these foods in all young age groups, and for high consumers in all age groups.
Improving Natural Killer Cancer Therapy
Vanderbilt University researchers discover transcription factor critical for NK cell expansion. Findings could lead to increased therapeutic efficacy.
Molecular Mechanism For Generating Specific Antibody Responses Discovered
Study could spur more ways to treat autoimmune disease, develop accurate vaccines.
Monovar Drills Down Into Cancer Genome
Rice, MD Anderson develop program to ID mutations in single cancer cells.
It’s Now Easier To Go With The Flow
Rice University tool simplifies comparison of flow cytometry data for laboratories.
Autism, Cancer Share a Remarkable Number of Risk Genes
Researchers with the UC Davis Comprehensive Cancer Center, MIND Institute identify more than 40 common genes.
Number Of Known Genetic Risk Factors For Endometrial Cancer Doubled
An international collaboration of researchers has identified five new gene regions that increase a woman’s risk of developing endometrial cancer, one of the most common cancers to affect women, taking the number of known gene regions associated with the disease to nine.
Scroll Up
Scroll Down
Skyscraper Banner

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
3,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,500+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!