Featured Research

from universities, journals, and other organizations

Gene-Silencing Technique Offers New Way To Fight Drug-Resistant Leukemia

Date:
November 4, 2004
Source:
University Of Pennsylvania Medical Center
Summary:
Ever since the approval of Gleevec in 2001, a cancer-cell-specific drug used to treat chronic myelogenous leukemia (CML), the field of cancer therapeutics has been rushing full speed into the era of so-called "targeted" medicines.

Philadelphia, PA) - Ever since the approval of Gleevec in 2001, a cancer-cell-specific drug used to treat chronic myelogenous leukemia (CML), the field of cancer therapeutics has been rushing full speed into the era of so-called "targeted" medicines. The challenge of developing these medicines, which spare normal cells because they are designed to kill only cancer cells, has been complicated by the recognition that resistance to even targeted therapies can develop. In the case of Gleevec, for example, which disables the BCR-ABL1 protein that causes CML, resistance has become a growing problem. Currently, physicians estimate that 5 percent to 10 percent of patients who begin treatment in the chronic phase of their disease will develop resistance to Gleevec; and if treatment is begun at more advanced stages of CML, this percentage is much higher.

Now researchers at the Abramson Cancer Center of the University of Pennsylvania have found a way around this problem. By disabling a BCR-ABL1-associated enzyme called Lyn kinase, they have induced cell death in drug-resistant CML cells taken from CML patients. Normal blood cells do not appear to be harmed by this approach because they are not so dependent on the Lyn kinase as CML cells. The Lyn kinase is therefore a good candidate for a targeted therapy.

“We know that patients treated with Gleevec can develop mutations in the BCR-ABL1 protein,” explains Alan M. Gewirtz, MD, Professor of Medicine in Penn’s Division of Hematology/Oncology. “Once the BCR-ABL1 gene mutates, Gleevec can no longer combine with the BCR-ABL1 protein, so it remains active, and the cancerous blood cells survive and grow." Gewirtz and colleagues’ research appears in the November issue of Nature Medicine.

"Lyn kinase is a member of a family of proteins that we know plays a role in cell survival, growth, and development," explains Gewirtz. “CML cells, especially those that arise in Gleevec-resistant patients, are very dependent on its function." To disable it, the researchers used short interfering RNA (siRNA) to "silence" the gene that codes for the Lyn kinase protein.

An siRNA is a short, double-stranded piece of RNA with a unique chemical sequence, or tag, that allows it to combine specifically with a particular messenger RNA (mRNA) that shares the same tag. After the siRNA is introduced into a cell it attaches to the mRNA whose tag it shares, and this targets the mRNA for destruction using a natural disposal system present in all cells. Without an mRNA to direct the production of Lyn kinase protein, the Lyn gene is effectively shut down, or "silenced." With Lyn out of the picture, the cancer cell dies.

“We hope that this therapy will be able to enter the clinic rapidly, perhaps even within the next couple of years,” say Gewirtz. “The basic methodologies are in place but an siRNA molecule still needs FDA approval.”

Andrezej Ptasznik, Yuji Nakata, Ann Kolata, and Stephen G. Emerson from Penn were all co-authors on the paper. This research was funded in part by grants from the Doris Duke Charitable Foundation, the National Institutes of Health, and the Leukemia and Lymphoma Society.


Story Source:

The above story is based on materials provided by University Of Pennsylvania Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

University Of Pennsylvania Medical Center. "Gene-Silencing Technique Offers New Way To Fight Drug-Resistant Leukemia." ScienceDaily. ScienceDaily, 4 November 2004. <www.sciencedaily.com/releases/2004/11/041104011726.htm>.
University Of Pennsylvania Medical Center. (2004, November 4). Gene-Silencing Technique Offers New Way To Fight Drug-Resistant Leukemia. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2004/11/041104011726.htm
University Of Pennsylvania Medical Center. "Gene-Silencing Technique Offers New Way To Fight Drug-Resistant Leukemia." ScienceDaily. www.sciencedaily.com/releases/2004/11/041104011726.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Liberia Pleads for Help to Fight Ebola

Liberia Pleads for Help to Fight Ebola

AP (Sep. 22, 2014) Liberia's finance minister is urging the international community to quickly follow through on pledges of cash to battle Ebola. Bodies are piling up in the capital Monrovia as the nation awaits more help. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Ebola Doctor Says Border Controls Critical

Ebola Doctor Says Border Controls Critical

AP (Sep. 22, 2014) A Florida doctor who helped fight the expanding Ebola outbreak in West Africa says the disease can be stopped, but only if nations quickly step up their response and make border control a priority. (Sept. 22) Video provided by AP
Powered by NewsLook.com
Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
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