Featured Research

from universities, journals, and other organizations

Resistance To Chemotherapy: How Tumors Acquire Resistance To Kinase Inhibitors

Date:
March 7, 2005
Source:
Public Library Of Science
Summary:
Acquired resistance to chemotherapy is a major obstacle to successful cancer treatment. Understanding the mechanisms by which tumors become resistant to a particular agent is key to identifying new drugs or combination regimens.

CT-guided biopsy of progressing lung lesions after 10 months on gefitinib. Photo: William Pao, et al.

Acquired resistance to chemotherapy is a major obstacle to successful cancer treatment. Understanding the mechanisms by which tumors become resistant to a particular agent is key to identifying new drugs or combination regimens. In an upcoming article in the international open-access journal PLoS Medicine, William Pao and colleagues (from the Memorial Sloan-Kettering Cancer Center in New York) shed light on what causes resistance to two recently approved lung cancer drugs.

Related Articles


The drugs are so-called kinase inhibitors and inhibit the epidermal growth factor receptor (EGFR) kinase molecule. Both of them, gefitinib (Iressa) and erlotinib (Tarceva), have shown therapeutic benefits in a subset of patients with lung cancer. Recent work has helped to understand why some patients respond and some don't: responsive tumors usually harbor activating mutations in the EGFR gene, which somehow make the tumors sensitive to treatment. Nearly all patients whose tumors initially respond to the drugs, however, eventually become resistant to the drugs and progress despite continued therapy.

In this study, the scientists examined tumors from six patients with non-small cell lung cancer who initially responded to gefitinib or erlotinib but subsequently relapsed. Tumors from all six patients carried activating mutations in the EGFR gene. In addition, in three out of the six cases, the resistant tumor cells carried an identical second mutation in the EGFR gene. Whereas the activating mutation was present in tumor cells before treatment with erlotinib or gefitinib, the second mutation was not found in pre-treatment biopsies from these patients, nor in over 150 lung cancer samples from patients who had not been treated with either drug. Additional cell culture studies supported the notion that the secondary mutation causes resistance to gefitinib or erlotinib. It is clear, though, that this is only one of several resistance mechanisms, because in the three other cases resistance occurred in the absence of the second mutation. What caused the resistance in those tumors is not known.

All kinases share some common features, and a resistance mutation very similar to the one identified here has also been found in other kinase genes from tumors with acquired resistance to imatinib, another kinase inhibitor. As Gary Gilliland and colleagues point out in an accompanying Perspective article, the initial identification three years ago of resistance mutations against imatinib led to the rapid development of alternative kinase inhibitors that work even against tumors with the resistance mutation. Similarly, the results by Pao and colleagues should help researchers develop second generation drugs for lung cancer.

###

Citation: Pao W, Miller VA, Politi KA, Riely GJ, Somwar R, et al. (2005) Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. 2(3): e73.


Story Source:

The above story is based on materials provided by Public Library Of Science. Note: Materials may be edited for content and length.


Cite This Page:

Public Library Of Science. "Resistance To Chemotherapy: How Tumors Acquire Resistance To Kinase Inhibitors." ScienceDaily. ScienceDaily, 7 March 2005. <www.sciencedaily.com/releases/2005/02/050224105956.htm>.
Public Library Of Science. (2005, March 7). Resistance To Chemotherapy: How Tumors Acquire Resistance To Kinase Inhibitors. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2005/02/050224105956.htm
Public Library Of Science. "Resistance To Chemotherapy: How Tumors Acquire Resistance To Kinase Inhibitors." ScienceDaily. www.sciencedaily.com/releases/2005/02/050224105956.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

Ebola-Hit Sierra Leone's Late Cocoa Leaves Bitter Taste

AFP (Nov. 23, 2014) The arable district of Kenema in Sierra Leone -- at the centre of the Ebola outbreak in May -- has been under quarantine for three months as the cocoa harvest comes in. Duration: 01:32 Video provided by AFP
Powered by NewsLook.com
WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Raw: Paralyzed Marine Walks With Robotic Braces

Raw: Paralyzed Marine Walks With Robotic Braces

AP (Nov. 21, 2014) Marine Corps officials say a special operations officer left paralyzed by a sniper's bullet in Afghanistan walked using robotic leg braces in a ceremony to award him a Bronze Star. (Nov. 21) 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