Navigation Links
Notch-blocking drugs kill brain cancer stem cells, yet multiple therapies may be needed
Date:2/25/2010

Working with mice, Johns Hopkins scientists who tested drugs intended to halt growth of brain cancer stem cells a small population of cells within tumors that perpetuate cancer growth conclude that blocking these cells may be somewhat effective, but more than one targeted drug attack may be needed to get the job done.

One focus of attack is a chemical pathway within stem cells known as Notch, which scientists have shown is important for cancer stem cell growth. A new study published in the January 28 issue of Stem Cells by Charles Eberhart, M.D., Ph.D., associate professor of pathology, ophthalmology, and oncology at Johns Hopkins, now extends these findings to glioblastoma, the most common malignant brain tumor, and ultimately suggests other pathways and treatment with two or more drugs may need to be involved.

Eberhart based his conclusion on experiments in which he coaxed a glioblastoma cell line to form embryolike balls called neurospheres. Unlike most cells that will clump together in a culture dish, neurospheres more organized groups of neural cells can only form from stem cells. When Eberhart treated the neurospheres with a drug called GSI-18, which blocks the Notch pathway, the spheres were reduced by 70 percent or more. Eberhart also found that molecular markers typically found on the surface of brain cancer stem cells also plunged.

"This told us that the Notch pathway is a good target for drug development," says Eberhart, but further experiments suggested this approach may not be thorough enough.

In a second set of experiments, Eberhart collected the neurospheres that remained after treatment with the Notch-blocking drug and injected them into the brains of mice. The neurosphere transplants eventually grew into tumors and reignited the Notch pathway.

"This result suggested we didn't get rid of all the stem cells," says Eberhart, "so it's likely we may need to add more therapies or increase the dosage of Notch-blocking drugs."

The study by Eberhart identified additional molecular pathways, including Stat 3 and AKT, which are connected to Notch. He says that a combination of therapies blocking Notch and other pathways such as these could target brain cancer stem cells at several levels and possibly avoid drug resistance.

To test how a Notch-blocking drug worked in an animal model, Eberhart injected tumors into the brains of mice and let the cancer grow for two weeks. Then, at the tumor site, he implanted a polymer bead that was soaked in GSI-18. Five of six mice that received the drug-laden bead survived while all 12 that received a bead with no drug died.

Eberhart notes that Notch-targeting drugs can prove problematic in therapy because the Notch pathway is critically important for cells in the gut, helping cells there alternate between secreting mucus and absorbing nutrients. "A dosing regimen that preserves gut function has been developed, and forthcoming studies in humans will test whether it can kill the cancer stem cells."


'/>"/>

Contact: Vanessa Wasta
wastava@jhmi.edu
410-955-1287
Johns Hopkins Medical Institutions
Source:Eurekalert

Related medicine news :

1. New review suggests caution on drugs to raise good cholesterol
2. Can cancer drugs combine forces?
3. Study provides hope that some transplant patients could live free of antirejection drugs
4. Study provides hope that some transplant patients could live free of anti-rejection drugs
5. RA Drugs Linked to Slight Skin Cancer Risk
6. Report on patients access to cancer drugs uses flawed methods to reached flawed conclusions
7. Rock N Roll: Sex, Drugs and an Early Exit
8. Australian-led international study shows blood pressure drugs cut death rate in type 2 diabetes
9. Consumer Reports Analysis: Drugs for Nerve Pain, Fibromyalgia Effective, But Not Always Best
10. Are Bargaining Groups Hired by Independent Drugstores Causing Payment Delays to Pharmacies?
11. 2 drugs equally effective for heart patients undergoing angioplasty, Mayo study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... ... March 23, 2017 , ... 82% of adults are unaware of the dangers that ... brush their teeth the minimum two times a day that dentists recommend. The ramifications of ... million hours of school and adults missing 164 million hours of work each year due ...
(Date:3/23/2017)... ... March 23, 2017 , ... ... Accreditation from the NCQA. The accreditation covers StayWell’s asthma, coronary artery disease, congestive ... is granted to organizations that have excellent programs for the delivery and improvement ...
(Date:3/23/2017)... ... 23, 2017 , ... Michael Lanteri Agency, an insurance and ... area, has unveiled a collaboration with nonprofit Big Bones Canine Rescue as the ... cause may now be made at http://bigbonescaninerescue.com/ . , Big Bones Canine ...
(Date:3/23/2017)... ... March 23, 2017 , ... ?This conference will prominently feature 150+ Hospital and Health System ... AMN Healthcare: Susan Salka , 43rd President of the United States of America: ... My Life In and Out of the Ring: Sugar Ray Leonard , JD, ...
(Date:3/23/2017)... ... March 23, 2017 , ... Natural Subsistence, a company known ... health and nutrition, announced its product Leyzene is now available for purchase on ... supplements that help people improve all aspects of their health so they can ...
Breaking Medicine News(10 mins):
(Date:3/23/2017)... SAO PAULO , March 23, 2017 ... accordance with article 157, paragraph 4 of Law 6,404/76 ... Commission (CVM), hereby informs its shareholders and the market ... jointly with its subsidiary Centro de Diagnosticos por Imagem ... acquisition of 100% interest in RADIOLOGISTAS ASSOCIADOS LTDA. (" ...
(Date:3/23/2017)... , March 23, 2017 Ascendis Pharma ... innovative TransCon technology to address significant unmet medical needs ... host a conference call and webcast on Monday, April ... Endocrine Society in Orlando, Florida , ... pipeline candidates (TransCon Growth Hormone, TransCon PTH and TransCon ...
(Date:3/23/2017)... , March 23, 2017 /PRNewswire/ - INVICTUS MD STRATEGIES ... FRA: 8IS) Invictus MD announces that AB Laboratories Inc. ... its licensed production facility under the Access to Cannabis ... Hamilton, Ontario . The facility, ... October 2016, is currently operating at half capacity, with ...
Breaking Medicine Technology: