Navigation Links
Selectively stopping glutathione sensitizes brain tumors to chemotherapy
Date:1/12/2012

Brain cancer cells are particularly resistant to chemotherapy toxins enter the cells, but before the toxins can kill, cancer cells quickly pump them back outside. In fact, brain cancer cells are even better than healthy cells at cleaning themselves. This means that when hit with chemotherapy, healthy cells tend to die before brain cancer cells. Especially in the brain, killing healthy cells is bad.

Researchers at the University of Colorado Cancer Center have discovered a way to turn off the pumps only in brain cancer cells and not in their healthy neighbors. Promising early testing provides hope for the nearly 45,000 people diagnosed with brain cancer in the United States every year, who are currently expected to survive less than 12 months after diagnosis.

The key is a chemical called glutathione (GSH).

The GSH pathway allows both healthy and cancerous cells to pump out toxins. The more GSH a cell makes, the more efficiently it can cleanse itself. Brain cancer cells may literally coat themselves with GSH, allowing them to pump out and thus survive doses of chemotherapy that quickly kill healthy brain cells. (This GSH pathway is the focus of a recent CU Cancer Center paper published in the journal Biochemical Pharmacology.)

But this same mechanism that makes brain cancer cells especially hearty may in fact be the key to their demise.

The idea is this: stop a cell's ability to make GSH and you stop its ability to detoxify thus sensitizing the cell to even a low dose of chemotherapy. It's tricky to target GSH directly, but clinical trials are already underway for a drug that breaks a link in the chain that leads to GSH. The link is an enzyme called glutamate cysteine ligase (GCL), which cells need in order to make GSH.

No GCL means no GSH, means a cell is doomed to stew in chemotherapy rather than pumping it out.

Unfortunately, the drug in clinical trials stops ALL cells healthy and cancerous from making GSH. And by so doing, it sensitizes both healthy and cancerous cells to chemotherapy. Killing everything more effectively does little good. (The same could be accomplished simply by giving a higher dose of chemotherapy.)

So here is the trick and the promise:

"If we can selectively keep brain tumor cells from making GSH we can sensitize these tumors to chemotherapy, which may allow doctors to kill more tumor cells with a safe dose of chemotherapeutics," says Christopher Franklin, PhD, investigator at the CU Cancer Center and assistant professor of molecular toxicology at the Skaggs School of Pharmacy and Pharmaceutical Sciences.

Franklin is working with Philip Reigan, PhD, investigator at the CU Cancer Center and assistant professor of medicinal chemistry at the Skaggs School of Pharmacy and Pharmaceutical Sciences to do just that targeting cancer cells' GSH while leaving the pathway unharmed in healthy cells.

To do it, they're using an exciting class of medicines called prodrugs. By itself a prodrug doesn't do anything it floats harmlessly through the body. Only, when it comes in contact with another target chemical the prodrug releases a little payload.

In this case, the prodrug payload is the drug that stops cells from making GSH. And the chemical that tells the prodrug to release its payload is an enzyme specific to brain cancer cells. This means that only when near brain cancer cells does the prodrug stop cells' ability to make GSH. Given along with chemotherapy, the prodrug should turn the table on brain cancer cells, making them die sooner than healthy neighbors.

"The current standard of care adds only about three months to the life expectancy of a patient diagnosed with glioblastoma multiforme," Reigan says. "The promise of prodrugs that selectively target tumor cells is not only exciting, but it's desperately needed for the treatment of brain tumors."


'/>"/>

Contact: Garth Sundem
garth.sundem@ucdenver.edu
University of Colorado Denver
Source:Eurekalert

Related medicine news :

1. Agent selectively targets malignant B cells in chronic leukemia, study shows
2. Researchers selectively control anxiety pathways in the brain
3. Hand-Washing Key to Stopping Spread of Disease
4. Some States Make Stopping Smoking Easier Than Others
5. Stopping dangerous cell regrowth reduces risk of further heart attacks
6. Stopping Daily Aspirin Boosts Heart Attack Risk: Study
7. ACP commends Congress for preserving patient access by stopping scheduled Medicare SGR cuts
8. Internists issue heartfelt plea for Congress to help patients by stopping Medicare SGR cuts
9. Researchers find new target for stopping tumors developing their own blood supply
10. Stopping smoking cessation treatments too soon may reduce odds of success for 45 percent of smokers
11. Non-IV-administered medication just as effective in stopping seizures
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/25/2016)... ... May 25, 2016 , ... DKT International, one of the ... is pleased to release their 2015 global impact data. In 2015, DKT served ... maternal deaths and 3.8 million unsafe abortions across 21 countries worldwide. , ...
(Date:5/25/2016)... ... May 25, 2016 , ... Conrad Siegel Actuaries, delivering comprehensive ... Prescription Drug survey , an employee benefits survey measuring how Central ... December 2015, indicates that employers are turning to consumer directed health care and ...
(Date:5/25/2016)... ... May 25, 2016 , ... "FCPX LUT Intense allows users to ... said Christina Austin - CEO of Pixel Film Studios. , With the FCPX ... add stylish color grades to their footage. A LUT is a Lookup Table that ...
(Date:5/25/2016)... Atlanta GA (PRWEB) , ... May 25, 2016 ... ... workplace solutions builder, has announced that it will join America's leading engineers at ... will be held at the Georgia World Congress Center. , Engineers, speakers ...
(Date:5/24/2016)... ... May 24, 2016 , ... BTC Media, ... blockchain event, Distributed: Health, to be held in Nashville, Tennessee on September 7, ... A 24-hour Hackathon preceding the event will host teams from around the world, ...
Breaking Medicine News(10 mins):
(Date:5/24/2016)... ARANZ Medical  Ltd a specialist ... has been named the Coretex Hi-Tech Emerging Company of the ... Dr Bruce Davey , CEO of ARANZ Medical says, ... good to be recognised for the work we are doing ... in 35 countries around the world from Sub-Saharan Africa through ...
(Date:5/24/2016)... , May 24, 2016 ... the world , s first dual ... fistula intervention   OrbusNeich, a global company ... expanded its portfolio to include products to treat peripheral ... the company,s first entry devices for lower limb and ...
(Date:5/24/2016)... 24, 2016 Dutch surgeons have launched a ... the world and treat patients on a global scale. Medical professionals ... Asia and the US have already signed ... and networking in a totally secure environment. Education  ... zone working together with a surgeon at Harvard to treat a ...
Breaking Medicine Technology: