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:6/23/2017)... ... ... All-Star Insurance, a family managed agency that offers insurance management assistance and personal ... of a new charity drive to benefit women in the area diagnosed with breast ... estimated 252, 710 new cases of invasive or high risk breast cancer will be ...
(Date:6/22/2017)... ... 2017 , ... Plastic Surgery Associates is proud to report that founding surgeon, ... research and information firm, Castle Connolly, releases their list of the most notable and ... 3rd time that Dr. Canales has been recognized by Castle Connolly. , ...
(Date:6/22/2017)... ... 2017 , ... Despite its pervasiveness, many physicians are unfamiliar with how best ... with clinical practice. Now, however, a timely review has been published in the ... etiology of NeuP and educating preclinical scientists on its diagnosis and choice of treatment. ...
(Date:6/22/2017)... ... June 23, 2017 , ... Rise Against Hunger ... June 21, 2017, at the Emeryville Center of Community Life. More than 374 ... world. , Rise Against Hunger (formerly Stop Hunger Now) meal packaging events are ...
(Date:6/20/2017)... , ... June 20, 2017 , ... After months of negotiations, FaceCradle USA is proud ... on Wednesday, June 21. , “Introducing our product on QVC is something we all ... promote our travel pillow to more than 90 million homes in the United States,” said ...
Breaking Medicine News(10 mins):
(Date:6/8/2017)... , June 8, 2017  Less than a month ... more than 200,000 companies, including hospital networks, in over ... as one of the largest online extortion attempts ever ... healthcare market, it is imperative that providers understand where ... data from this — and many other very real ...
(Date:6/7/2017)... Iowa , June 6, 2017  Diplomat Specialty Infusion Group, ... sterile compounding environment to its Iowa location. ... Urbandale now features an ISO 7 cleanroom—the standard ... controlled environment with a low level of pollutants. ... more IV nutrition consumers and better serve our Iowa ...
(Date:6/1/2017)... 1, 2017 Nutriceutical Holdings (NH), parent company ... (VRS), and KD Pharma Group have decided to join ... KD Pharma Group. KD Pharma Group will become the ... acquire the entire company. "We believe we ... committed to growing the NH companies by providing us ...
Breaking Medicine Technology: