Featured Research

from universities, journals, and other organizations

Common genetic pathway could be conduit to pediatric tumor treatment

Date:
November 7, 2013
Source:
Johns Hopkins Medicine
Summary:
Investigators have found a known genetic pathway to be active in many difficult-to-treat pediatric brain tumors called low-grade gliomas, potentially offering a new target for the treatment of these cancers.

Investigators at Johns Hopkins have found a known genetic pathway to be active in many difficult-to-treat pediatric brain tumors called low-grade gliomas, potentially offering a new target for the treatment of these cancers.

In laboratory studies, researchers found that the pathway, called mammalian target of rapamycin (mTOR), was highly active in pediatric low-grade gliomas, and that mTOR activity could be blocked using an experimental drug, leading to decreased growth of these tumors.

"We think mTOR could function as an Achilles heel," says study co-author Eric Raabe, M.D., Ph.D., an assistant professor of pediatrics, oncology and pathology at the Johns Hopkins Kimmel Cancer Center. "It drives cancer growth, but when mTOR is inhibited, the tumor falls apart." The work was described Nov. 7 in the journal Neuro-Oncology.

Overall, brain tumors affect more than 4,000 children each year in the United States, and they are the leading cause of cancer deaths in children, according to Raabe. Low-grade gliomas are the most common group of tumors of the central nervous system in children. Current treatments for these tumors include surgery and chemotherapy, which often cause significant side effects. Many of these tumors are located in areas like the optic pathway, where they can't be easily removed by surgery without causing damage, including blindness. In addition to vision loss, some of Raabe's patients have endured paralysis or learning problems as a result of the tumor or treatment.

"Even though these tumors are considered 'low grade' and not particularly aggressive, many patients suffer severe, life-altering symptoms, so we desperately need better therapies," says Raabe.

For the study, the Johns Hopkins investigators studied tissue samples from 177 pediatric low-grade gliomas, including the most common type -- tumors called pilocytic astrocytomas -- from patients treated at Johns Hopkins and other centers. They also tested the effect of blocking mTOR with an investigational agent known as MK8669 (ridaforolimus) in two pediatric low-grade glioma cell lines.

The mTOR pathway has been shown to be active in a variety of cancers, and drugs that block proteins in the pathway, such as rapamycin, are widely available. The pathway signals through two protein complexes, mTORC1 and mTORC2, which lead to increased cell growth and survival.

The researchers found activity of the mTORC1 pathway in 90 percent of low-grade gliomas studied, and 81 percent of tumors showed activity of both mTORC1 and mTORC2. Components of the mTOR pathway were more commonly found in tumors from optic pathways compared with those from other areas of the brain, according to Fausto Rodriguez , M.D., senior study author and assistant professor of pathology and oncology at Johns Hopkins.

The scientists also found that the mTOR-blocking drug caused up to a 73 percent reduction in cell growth over six days in one cell line, and up to a 21 percent decrease in cell growth over four days in a second cell line.

"Since the pathways are more active in some areas of the brain, compared with others, it suggests that the outcomes of drug treatments targeting those pathways may differ as well," says Rodriguez.

Rodriguez and Raabe say they hope to build on the research in animal models and test additional inhibitors.


Story Source:

The above story is based on materials provided by Johns Hopkins Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Marianne Hütt-Cabezas, Matthias A. Karajannis, David Zagzag, Smit Shah, Iren Horkayne-Szakaly, Elisabeth J. Rushing, J. Douglas Cameron, Deepali Jain, Charles G. Eberhart, Eric H. Raabe, and Fausto J. Rodriguez. Activation of mTORC1/mTORC2 signaling in pediatric low-grade glioma and pilocytic astrocytoma reveals mTOR as a therapeutic target. Neuro-Oncology, November 2013

Cite This Page:

Johns Hopkins Medicine. "Common genetic pathway could be conduit to pediatric tumor treatment." ScienceDaily. ScienceDaily, 7 November 2013. <www.sciencedaily.com/releases/2013/11/131107093828.htm>.
Johns Hopkins Medicine. (2013, November 7). Common genetic pathway could be conduit to pediatric tumor treatment. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2013/11/131107093828.htm
Johns Hopkins Medicine. "Common genetic pathway could be conduit to pediatric tumor treatment." ScienceDaily. www.sciencedaily.com/releases/2013/11/131107093828.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Residents Vaccinated as Haiti Fights Cholera Epidemic

Residents Vaccinated as Haiti Fights Cholera Epidemic

AFP (Sep. 18, 2014) — Haitians receive the second dose of the vaccine against cholera as part of the UN's vaccination campaign. Duration: 00:34 Video provided by AFP
Powered by NewsLook.com
Artificial Sweetener Could Promote Diabetes

Artificial Sweetener Could Promote Diabetes

Newsy (Sep. 17, 2014) — Doctors once thought artificial sweeteners lacked the health risks of sugar, but a new study says they can impact blood sugar levels the same way. Video provided by Newsy
Powered by NewsLook.com
Ebola Vaccine Trial Gets Underway at Oxford University

Ebola Vaccine Trial Gets Underway at Oxford University

AFP (Sep. 17, 2014) — A healthy British volunteer is to become the first person to receive a new vaccine for the Ebola virus after US President Barack Obama called for action against the epidemic and warned it was "spiralling out of control." Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) — Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins