Featured Research

from universities, journals, and other organizations

Combination Of Two Novel Anti-cancer Agents May Help Fight CML Resistant To Current Therapy

Date:
June 1, 2008
Source:
Virginia Commonwealth University
Summary:
Researchers have identified that a combination of novel anti-cancer compounds is able to kill chronic myelogenous leukemia cells previously resistant to conventional forms of therapy.

Virginia Commonwealth University Massey Cancer Center researchers have identified that a combination of novel anti-cancer compounds is able to kill chronic myelogenous leukemia cells previously resistant to conventional forms of therapy.

Related Articles


Chronic myelogenous leukemia, or CML, is a cancer of the bone marrow caused by a specific genetic abnormality and is one of the more common forms of leukemia. Imatinib mesylate, or Gleevec, is a highly effective anti-cancer agent that has revolutionized the course of therapy for patients with CML. It works by inhibiting the activity of a mutant protein, known as Bcr/Abl, which is responsible for the disease. However, despite initial success, patients eventually become resistant to imatinib mesylate, often through the development of further mutations in the Bcr/Abl protein.

According to Steven Grant, M.D., Massey's associate director for translational research and co-leader of the cancer center's cancer cell biology program, and senior author of the study, resistance to imatinib mesylate prompted the search for newer agents that are active against the mutated forms of Bcr/Abl. Such agents include MK-0457, a Bcr/Abl kinase inhibitor that also targets another protein called an aurora kinase. Aurora kinase plays an important role in mitosis and cell division. In preclinical studies, MK-0457 is active against the T315I Bcr/Abl mutation, a major cause of imatinib resistance, and has shown promise in early clinical trials, Grant said.

In this study, Grant and colleagues examined the effects of combining MK-0457 with vorinostat, a novel targeted agent that has recently been approved for the treatment of cutaneous T-cell lymphoma. They found that this combination leads to a dramatic induction of apoptosis, or programmed cell death in CML cells, including imatinib-resistant cells bearing the T315I or other mutations. The article was pre-published as a First Edition Paper in Blood, the journal of the American Society of Hematology, which appeared online May 27.

Further, Grant said that the interaction between these agents may occur at multiple levels, including potentiation of Bcr/Abl inhibition as well as enhanced disruption of aurora kinase and mitosis. In addition, the group demonstrated that vorinostat-mediated up-regulation of Bim, a pro-apoptotic protein, contributed significantly to the effectiveness of this regimen.

"Our findings suggest it may be possible to develop a clinical regimen combining a third-generation Bcr/Abl kinase and aurora kinase inhibitor, such as MK-0457, with histone deacetylase inhibitors, such as vorinostat," Grant said.

"Theoretically, this combination could improve upon the results of Bcr/Abl kinase inhibitors administered alone, particularly in the case of imatinib-resistant disease," he said. Further preclinical studies are underway to test this hypothesis.

This work was supported by grants from the National Institutes of Health, the Leukemia and Lymphoma Society of America, the V Foundation, and the Department of Defense. Merck Pharmaceuticals supplied the agents tested in the preclinical studies.

Grant, who is a professor of medicine and the Shirley Carter and Sture Gordon Olsson Professor of oncology, worked with a team that included: Yun Dai, Ph.D., Shuang Chen, Ph.D., Charis A. Venditti, Xin-Yan Pei, Ph.D., and Tri K. Nguyen, Ph.D., all in the VCU Department of Medicine; and Paul Dent, Ph.D., a professor in the VCU Department of Biochemistry.


Story Source:

The above story is based on materials provided by Virginia Commonwealth University. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Commonwealth University. "Combination Of Two Novel Anti-cancer Agents May Help Fight CML Resistant To Current Therapy." ScienceDaily. ScienceDaily, 1 June 2008. <www.sciencedaily.com/releases/2008/05/080529124823.htm>.
Virginia Commonwealth University. (2008, June 1). Combination Of Two Novel Anti-cancer Agents May Help Fight CML Resistant To Current Therapy. ScienceDaily. Retrieved December 21, 2014 from www.sciencedaily.com/releases/2008/05/080529124823.htm
Virginia Commonwealth University. "Combination Of Two Novel Anti-cancer Agents May Help Fight CML Resistant To Current Therapy." ScienceDaily. www.sciencedaily.com/releases/2008/05/080529124823.htm (accessed December 21, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, December 21, 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