Featured Research

from universities, journals, and other organizations

Researchers uncover a genetic vulnerability of lung cancer to lay the foundation for new drug options

Date:
April 4, 2013
Source:
UT Southwestern Medical Center
Summary:
Physician-researchers at UT Southwestern have identified a vulnerability of certain lung-cancer cells – a specific genetic weakness that can be exploited for new therapies.

Dr. Pier Paolo Scaglioni, assistant professor of internal medicine and a member of the Harold C. Simmons Cancer Center
Credit: Image courtesy of UT Southwestern Medical Center

Physician-researchers at UT Southwestern Medical Center have identified a vulnerability of certain lung-cancer cells -- a specific genetic weakness that can be exploited for new therapies.

Although researchers have long known that mutant versions of the KRAS gene drive tumor formation and are key to cell survival in non-small cell lung cancer, the blocking of activated KRAS has proven difficult. For years, investigations have explored stopping lung cancer at this junction, which also would have an impact on many other cancers. KRAS mutations, for instance, account for as much as 50 percent of all colon cancers.

"There is an urgent need to identify 'downstream' pathways that are required to sustain and grow non-small cell lung cancer (NSCLC)," said Dr. Pier Paolo Scaglioni, assistant professor of internal medicine and a member of the Harold C. Simmons Cancer Center. "As we focus on the right pathways, we stand a much better chance of chemically blocking them and stopping tumor growth."

The team's findings are published in the April edition of Cancer Discovery, a journal of the American Association for Cancer Research. Dr. Scaglioni served as senior author and Dr. Georgia Konstantinidou, a postdoctoral researcher, was first author.

To identify vulnerabilities in KRAS-mutant tumors, Dr. Scaglioni's group used a mouse model of high-grade lung adenocarcinoma induced by a recombinant transgene that allows activation of mutant KRAS in the respiratory epithelium. This strategy allows the generation of high-grade lung cancers that closely resemble human tumors.

Compared with control tumors, the investigators found that the protein RHOA was specifically required for the survival and growth of high-grade tumors via activation of a focal adhesion kinase (FAK). Consistent with a critical role for this pathway in NSCLC, activation of RHOA and FAK was observed in human NSCLC samples and human lung-cancer cells were found to be highly sensitive to pharmacologic inhibitors of FAK.

FAK is a protein that helps cells stick to each other and their surroundings, and also aids in determining how rigid and mobile the cell's structure is. When FAK is blocked in breast cancer, the cancer cells become less metastastic due to decreased mobility.

Dr. Scaglioni and his team are now poised to study in clinical trials the pharmacologic blockade of FAK using inhibitor compounds currently under commercial development.

"Our findings provide the rationale for the rapid implementation of genotype-specific targeted therapies utilizing FAK inhibitors in cancer patients," Dr. Konstantinidou said.

Other researchers at UT Southwestern involved in the paper include Dr. Rolf A. Brekken, associate professor of surgery and pharmacology; Dr. Michael T. Dellinger, postdoctoral researcher II in the Nancy B. and Jake L. Hamon Center for Therapeutic Oncology Research; and Rachel E. Ramirez, research assistant I in obstetrics/gynecology. Scientists from the University of Texas MD Anderson Cancer Center in Houston and Memorial Sloan-Kettering Cancer Center in New York also contributed to the investigation.

The research was conducted with support from the American Cancer Society, the Ryan Gibson Foundation, and the Department of Defense.


Story Source:

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


Journal Reference:

  1. G. Konstantinidou, G. Ramadori, F. Torti, K. Kangasniemi, R. E. Ramirez, Y. Cai, C. Behrens, M. T. Dellinger, R. A. Brekken, I. I. Wistuba, A. Heguy, J. Teruya-Feldstein, P. P. Scaglioni. RHOA-FAK Is a Required Signaling Axis for the Maintenance of KRAS-Driven Lung Adenocarcinomas. Cancer Discovery, 2013; DOI: 10.1158/2159-8290.CD-12-0388

Cite This Page:

UT Southwestern Medical Center. "Researchers uncover a genetic vulnerability of lung cancer to lay the foundation for new drug options." ScienceDaily. ScienceDaily, 4 April 2013. <www.sciencedaily.com/releases/2013/04/130404072244.htm>.
UT Southwestern Medical Center. (2013, April 4). Researchers uncover a genetic vulnerability of lung cancer to lay the foundation for new drug options. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2013/04/130404072244.htm
UT Southwestern Medical Center. "Researchers uncover a genetic vulnerability of lung cancer to lay the foundation for new drug options." ScienceDaily. www.sciencedaily.com/releases/2013/04/130404072244.htm (accessed July 25, 2014).

Share This




More Health & Medicine News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

New Painkiller Designed To Discourage Abuse: Will It Work?

New Painkiller Designed To Discourage Abuse: Will It Work?

Newsy (July 24, 2014) The FDA approved Targiniq ER on Wednesday, a painkiller designed to keep users from abusing it. Like any new medication, however, it has doubters. Video provided by Newsy
Powered by NewsLook.com
Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Doctor At Forefront Of Fighting Ebola Outbreak Gets Ebola

Newsy (July 24, 2014) Sheik Umar Khan has treated many of the people infected in the Ebola outbreak, and now he's become one of them. Video provided by Newsy
Powered by NewsLook.com
Condemned Man's US Execution Takes Nearly Two Hours

Condemned Man's US Execution Takes Nearly Two Hours

AFP (July 24, 2014) America's death penalty debate raged Thursday after it took nearly two hours for Arizona to execute a prisoner who lost a Supreme Court battle challenging the experimental lethal drug cocktail. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com
Can Watching TV Make You Feel Like A Failure?

Can Watching TV Make You Feel Like A Failure?

Newsy (July 24, 2014) A study by German researchers claims watching TV while you're stressed out can make you feel guilty and like a failure. 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:
from the past week

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