Featured Research

from universities, journals, and other organizations

Study reveals new molecular target for melanoma treatment

Date:
August 17, 2012
Source:
University of North Carolina Health Care
Summary:
A laboratory study demonstrates how a new targeted drug, Elesclomol, blocks oxidative phosphorylation, which appears to play essential role in melanoma that has not been well understood. Elesclomol was previously shown to have clinical benefit only in patients with normal serum lactate dehydrogenase, a laboratory test routinely used to assess activity of disease.

A laboratory study led by UNC medical oncologist Stergios Moschos, MD, demonstrates how a new targeted drug, Elesclomol, blocks oxidative phosphorylation, which appears to play essential role in melanoma that has not been well-understood. Elesclomol (Synta Pharmaceuticals, Lexington, MA) was previously shown to have clinical benefit only in patients with normal serum lactate dehydrogenase (LDH), a laboratory test routinely used to assess activity of disease.

Related Articles


For more than 60 years, scientists have known that cancer cells undergo glycolysis, or metabolize glucose, at a much higher rate than normal cells. The observation, called the Warburg effect, demonstrated that the normal energy producing processes in the cell are disrupted in cancer cells, preventing them from using metabolic pathways in the cell's mitochondria (often called the cell's "power plants").

Recently, however, increasing evidence suggests that, in addition to glycolysis, other metabolic pathways may also play a role in cancer, with important therapeutic implications. A promising strategy for targeting cancer cells, while sparing normal cells, is to target these altered metabolic processes with drug therapies. Elesclomol has been shown to trigger cell death in metastatic melanoma cells, primarily by suppressing oxidative phosphorylation -- the process that cells use to transform nutrients into energy.

Moschos and his team demonstrated in the lab that metastatic melanoma cells exhibit a higher rate of glycolysis compared to their normal counterpart cells, termed melanocytes, which would be expected due to the Warburg effect.

"But we also found, surprisingly, that these cells have higher rates of oxidative phosphorylation -- they are producing energy through more than one pathway, which explains a lot about how the drug works," says Dr. Moschos.

He notes that this drug has an interesting history. In a 600-patient phase III clinical trial conducted almost 4 years ago, Elesclomol had clinical benefit in the subgroup of patients with normal serum LDH. However, the FDA discontinued the trial, because the Elesclomol in combination with another chemotherapeutic drug may have negative effects in patients with high serum LDH, which is associated with poorer patient outcomes in metastatic melanoma. At the time, very little was known about Elesclomol's mechanism of action -- blocking oxidative phosphorylation.

"Our inability to show how Elesclomol worked through measurement of biomarkers was the major driver to conduct this laboratory study," said Moschos, whose team took the clinical trial results back to the lab to try to figure out why the drug worked.

"Our results suggest that targeting oxidative phosphorylation in melanoma is a promising strategy for early metastatic disease, before melanoma cells switch their primary metabolic source to glycolysis, as Otto Warburg showed 60 years ago" said Dr. Moschos.

"Second, we were able to demonstrate a mechanism of resistance to Elesclomol, where long-term exposure to the drug leads to the selection of melanoma cells with high levels of glycolysis. This suggests that a two-pronged strategy aimed at blocking both metabolic pathways may be called for."

The results of the study were published August 17 in the journal Public Library of Science One.


Story Source:

The above story is based on materials provided by University of North Carolina Health Care. Note: Materials may be edited for content and length.


Cite This Page:

University of North Carolina Health Care. "Study reveals new molecular target for melanoma treatment." ScienceDaily. ScienceDaily, 17 August 2012. <www.sciencedaily.com/releases/2012/08/120817203919.htm>.
University of North Carolina Health Care. (2012, August 17). Study reveals new molecular target for melanoma treatment. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2012/08/120817203919.htm
University of North Carolina Health Care. "Study reveals new molecular target for melanoma treatment." ScienceDaily. www.sciencedaily.com/releases/2012/08/120817203919.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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