Featured Research

from universities, journals, and other organizations

New Drug May Be Formidable Adversary For Hard To Treat Leukemia

Date:
February 28, 2005
Source:
Cell Press
Summary:
As scientists uncover the precise molecular mechanisms that underlie effective cancer treatments, they gain invaluable insight into why predominantly successful treatments fail for some patients. A new study published in the February issue of Cancer Cell reveals how detailed information about the action of an existing drug was used to design a compound that is effective against some notoriously treatment resistant cancer cases.

As scientists uncover the precise molecular mechanisms that underlie effective cancer treatments, they gain invaluable insight into why predominantly successful treatments fail for some patients. A new study published in the February issue of Cancer Cell reveals how detailed information about the action of an existing drug was used to design a compound that is effective against some notoriously treatment resistant cancer cases.

Related Articles


Despite the resounding success of anticancer drug imatinib (Gleevec) as a treatment of chronic myeloid leukemia (CML), a small but growing number of patients develop resistance to the drug and relapse. Imatinib inhibits the activity of Bcr-Abl, a protein that is abnormally active in most CML patients. Relapse and resistance to imatinib in patients with advanced disease is linked to the emergence of additional mutant forms of Bcr-Abl that are not inhibited by imatinib.

A group led by Dr. James D. Griffin from the Dana-Farber Cancer Institute working with scientists at Novartis Pharma AG in Switzerland used data obtained from structural examination of the molecular interaction between imatinib and Abl to design AMN107, a compound that has a stronger and more complete molecular association with Abl. AMN107 effectively blocked proliferation of Bcr-Abl dependent cells derived from CML patients and was an even more potent inhibitor of Bcr-Abl than imatinib. Importantly, AMN107 inhibited the growth of cells expressing many Bcr-Abl mutants that were resistant to imatinib and oral administration of AMN107 prolonged survival in imatinib-resistant CML mouse models.

Phase I clinical trials with AMN107 have just started. "If human clinical trials validate the effectiveness of AMN107 demonstrated in the preclinical studies reported here, it may be possible to either use AMN107 in selected patients with imatinib resistance, or to use both agents together, simultaneously or sequentially," says Dr. Griffin. The researchers are hopeful that combined therapy may suppress emergence of treatment resistant Abl mutants and that availability of novel, high potency, Abl tyrosine kinase inhibitors will usher in a new generation of clinical studies that may result in additional major advances in the therapy of hard to treat leukemia.

###

Ellen Weisberg, Paul W. Manley, Werner Breitenstein, Josef Brüggen, Sandra W. Cowan-Jacob, Arghya Ray, Brian Huntly, Doriano Fabbro, Gabriele Fendrich, Elizabeth Hall-Meyers, Andrew L. Kung, Jürgen Mestan, George Q. Daley, Linda Callahan, Laurie Catley, Cara Cavazza, Azam Mohammed, Donna Neuberg, Renee D. Wright, D. Gary Gilliland, and James D. Griffin: "Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl"

The researchers included Ellen Weisberg, Arghya Ray, Elizabeth Hall-Meyers, Linda Callahan, Laurie Catley, Cara Cavazza, Donna Neuberg, and James D. Griffin of Dana-Farber Cancer Institute in Boston; Paul W. Manley, Werner Breitenstein, Josef Brüggen, Sandra W. Cowan-Jacob, Doriano Fabbro, Gabriele Fendrich, and Jürgen Mestan of Novartis Institutes for Biomedical Research in Basel; Brian Huntly, Renee D. Wright, and D. Gary Gilliland of Brigham and Women's Hospital in Boston; Andrew L. Kung of Dana-Farber Cancer Institute and Children's Hospital in Boston; and George Q. Daley and Azam Mohammed of Children's Hospital in Boston. This research was supported by NIH grants, a Specialized Center of Research Award from the Leukemia and Lymphoma Society, grants from the National Cancer Institute, the NIH Director's Pioneer Award and the Burroughs Wellcome Fund. P.W.M., W.B., J.B., S.W.C.-J., D.F., G.F., and J.M. are employees of Novartis Pharma AG, Basel, Switzerland. J.D.G has a financial interest with Novartis Pharma AG.

Publishing in Cancer Cell, Volume 7, Number 2, February 2005, pages 129-141. http://www.cancercell.org/


Story Source:

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


Cite This Page:

Cell Press. "New Drug May Be Formidable Adversary For Hard To Treat Leukemia." ScienceDaily. ScienceDaily, 28 February 2005. <www.sciencedaily.com/releases/2005/02/050218131439.htm>.
Cell Press. (2005, February 28). New Drug May Be Formidable Adversary For Hard To Treat Leukemia. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2005/02/050218131439.htm
Cell Press. "New Drug May Be Formidable Adversary For Hard To Treat Leukemia." ScienceDaily. www.sciencedaily.com/releases/2005/02/050218131439.htm (accessed November 28, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, November 28, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Leaves Orphans Alone in Sierra Leone

Ebola Leaves Orphans Alone in Sierra Leone

AFP (Nov. 27, 2014) — The Ebola epidemic sweeping Sierra Leone is having a profound effect on the country's children, many of whom have been left without any family members to support them. Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Experimental Ebola Vaccine Shows Promise In Human Trial

Experimental Ebola Vaccine Shows Promise In Human Trial

Newsy (Nov. 27, 2014) — A recent test of a prototype Ebola vaccine generated an immune response to the disease in subjects. Video provided by Newsy
Powered by NewsLook.com
Pet Dogs to Be Used in Anti-Ageing Trial

Pet Dogs to Be Used in Anti-Ageing Trial

Reuters - Innovations Video Online (Nov. 26, 2014) — Researchers in the United States are preparing to discover whether a drug commonly used in human organ transplants can extend the lifespan and health quality of pet dogs. Video provided by Reuters
Powered by NewsLook.com
Today's Prostheses Are More Capable Than Ever

Today's Prostheses Are More Capable Than Ever

Newsy (Nov. 26, 2014) — Advances in prosthetics are making replacement body parts stronger and more lifelike than they’ve ever been. Video provided by Newsy
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