Featured Research

from universities, journals, and other organizations

Researchers Uncover Mutated Genes Involved In Lung Cancer; One Affects Nonsmokers

Date:
March 10, 2005
Source:
University Of Texas Southwestern Medical Center At Dallas
Summary:
Lung cancer patients who have never smoked are more likely than smokers to harbor one of two genetic mutations that researchers at UT Southwestern Medical Center have now linked to the disease.

Drs. John Minna (left), director of the Hamon Center for Therapeutic Oncology Research, and Adi Gazdar, professor of pathology in the Hamon Center, have found that mutations in either of two genes are involved in lung cancer.
Credit: Photo courtesy of UT Southwestern Medical Center At Dallas

DALLAS - March 1, 2005 - Lung cancer patients who have never smoked are more likely than smokers to harbor one of two genetic mutations that researchers at UT Southwestern Medical Center have now linked to the disease. "This study describes the first known mutation to occur in lung cancer patients who have never smoked," said Dr. Adi Gazdar, professor of pathology in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research and senior author of the study in today's issue of the Journal of the National Cancer Institute. "These findings may help explain why certain lung cancer patients respond dramatically to a specific form of targeted therapy while others have little or no response."

Related Articles


Mutations in the epidermal growth factor receptor (EGFR) gene are present mainly in adenocarcinomas, the most common form of lung cancer found in smokers and non-smokers, as well in women and people under 45. These mutations have shown increased sensitivity to gefitinib (Iressa) and erlotinib (Tarceva), drugs targeting the gene.

To understand better the role of the EGFR mutation in the development of lung cancer, Dr. Gazdar and his colleagues analyzed tissue samplesfrom primary tumors of 519 patients in the United States, Japan, Taiwan and Australia. Mutations in the DNA of nonmalignant lung tissue from many of these patients and from other separate cancer tissues also were examined.

The researchers found mutations in the EGFR gene were much more common:

* in people with lung cancer who never smoked compared to smokers (51 percent vs. 10 percent, 85 of 166 nonsmokers vs. 35 of 353 smokers); * in adenocarcinomas compared to other lung cancers (40 percent vs. 3 percent, 114 of 289 adenocarcinomas vs. 6 of 230 other cancers); * in women compared to men (42 percent vs. 14 percent, 72 of 171 women vs. 48 of 348 men); * in patients of Asian ancestry compared to other ethnicities (30 percent vs. 8 percent, 107 of 361 Asians vs. 13 of 158 in other ethnicities).

Mutations in the KRAS gene - a gene in the EGFR signaling pathway - were found in8 percent of lung cancers but in none with the EGFR mutation. This mutation was more common in males, Caucasians, and current or former smokers.

As a result, it appears that two distinct molecular pathways are involved in formation of lung cancer, Dr. Gazdar said. The pathway in smokers involves KRAS gene mutations, while the pathway in people who never smoked involves EGFR gene mutations.

The next step is to move these findings toward development of better treatments for lung cancer, said Dr. Gazdar.

He and Dr. John Minna, director of the W.A. "Tex" and Deborah Moncrief Jr. Center for Cancer Genetics and the Hamon Center for Therapeutic Oncology Research and a contributing author, have established eight lung cancer cell lines that harbor several types of EGFR mutations and are now establishing another line from a patient who relapsed after initially responding well to the gefitinib drug.

"These lines will prove invaluable in understanding both the response to gefitinib and erlotinib and the mechanisms by which resistance eventually develops," Dr. Gazdar said. "The cell lines may help identify strategies to overcome this drug resistance that eventually develops in most responders."

A related study in the current issue of Cancer Research with Dr. Gazdar and his colleagues found that mutations in EGFR and HER2, another gene in the EGFR pathway that is associated with certain cancers, targeted the same patient subpopulations. The discovery that HER2 also is a mutation occurring mainly in tumors of people who never smoked suggests different pathways may be involved in lung cancer formation in smokers and nonsmokers.

"Our work is very important because if you have a mutation in the EGFR gene in the tumor, a patient likely will have a dramatic response to a relatively nontoxic once-daily oral therapy," Dr. Minna said. "The research has found these tumors can vary by several thousandfold on how sensitive they are to a drug," said Dr. Minna. "We also have been able to identify in advance a pattern of gene expression that tells whether a tumor is going to be resistant or sensitive to a particular drug. We want to be capable of examining a patient's tumor, profile each human gene and then select the best current therapy."

Dr. Minna and Dr. Jonathan Dowell, assistant professor of internal medicine, contributed to an editorial in the Feb. 24 issue of The New England Journal of Medicine commenting on a study headed by Dana Farber Cancer Research Center. Researchers there found a lung cancer that initially was very sensitive to gefitinib because of a mutation in the EGFR gene developed resistance to the drug because of a second EGFR mutation.

The enhanced understanding of EGFR and these mutations reported in the NEJM study will allow new drugs to be designed to combat these drug-resistant receptors, enabling effective second-line therapy to then be directed at the same target, Dr. Minna wrote.

Other UT Southwestern contributors to the JNCI study were Dr. Joachim Herz, professor of molecular genetics in the Center for Basic Neuroscience; Dr. Hisayuki Shigematsu and Dr. Masaharu Nomura, postdoctoral researchers, and Dr. Takao Takahashi, former postdoctoral researcher, all in the Hamon Center for Therapeutic Oncology Research. Researchers from UT M.D. Anderson Cancer Center in Houston also contributed, as well as investigators in Seattle, Japan, Taiwan and Australia.

Research was supported by grants from the NCI and Bristol-Myers Squibb.


Story Source:

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


Cite This Page:

University Of Texas Southwestern Medical Center At Dallas. "Researchers Uncover Mutated Genes Involved In Lung Cancer; One Affects Nonsmokers." ScienceDaily. ScienceDaily, 10 March 2005. <www.sciencedaily.com/releases/2005/03/050309104416.htm>.
University Of Texas Southwestern Medical Center At Dallas. (2005, March 10). Researchers Uncover Mutated Genes Involved In Lung Cancer; One Affects Nonsmokers. ScienceDaily. Retrieved November 24, 2014 from www.sciencedaily.com/releases/2005/03/050309104416.htm
University Of Texas Southwestern Medical Center At Dallas. "Researchers Uncover Mutated Genes Involved In Lung Cancer; One Affects Nonsmokers." ScienceDaily. www.sciencedaily.com/releases/2005/03/050309104416.htm (accessed November 24, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, November 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Winter Can Cause Depression — Here's How To Combat It

Winter Can Cause Depression — Here's How To Combat It

Newsy (Nov. 23, 2014) Millions of American suffer from seasonal depression every year. It can lead to adverse health effects, but there are ways to ease symptoms. Video provided by Newsy
Powered by NewsLook.com
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
Don't Fall For Flu Shot Myths

Don't Fall For Flu Shot Myths

Newsy (Nov. 23, 2014) Misconceptions abound when it comes to your annual flu shot. Medical experts say most people older than 6 months should get the shot. Video provided by Newsy
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

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