Featured Research

from universities, journals, and other organizations

Synthetic compound may lead to drugs to fight pancreatic, lung cancer

Date:
March 10, 2011
Source:
UT Southwestern Medical Center
Summary:
Researchers have identified a chemical compound that may eventually lead to a drug that fights cancers that are dependent on a particular anti-viral enzyme for growth.

Researchers at UT Southwestern Medical Center have identified a chemical compound that may eventually lead to a drug that fights cancers that are dependent on a particular anti-viral enzyme for growth.

The researchers are testing the compound's effectiveness at fighting tumors in mice. If it is successful, they will then work to develop a drug based on the compound to combat pancreatic and non-small cell lung cancer, two cancer types in which this particular enzyme, TBK-1, often is required for cancer cell survival.

"Our prediction is that TBK-1 is a good pharmacological intervention target for a subset of lung and pancreas cancers that are addicted to the activity of this enzyme. We believe there is a large population of cancer patients that could respond to inhibition of this activity," said Dr. Michael White, professor of cell biology and senior author of the study in the Feb. 18 issue of Molecular Cell.

The investigation, which lasted three and a half years, revealed how activation of the natural virus-fighting protein TBK-1 is hijacked in cancer cells to support growth and survival.

More than 250,000 compounds were screened to find one that would inhibit the enzyme's cancer-protection mechanism. The most effective, a compound called 6-aminopyrazolopyrimidine developed in collaboration with pharmaceutical company Amgen, blocked TBK-1's effects in 40 percent to 50 percent of the non-small cell lung cancer and pancreatic cancer tissue cultures tested, reducing cancer growth. TBK-1 is activated by the Ras family of oncogenes, which are mutated in 40 percent of lung cancers and 90 percent of pancreatic cancers.

"We found a biological activity that some cancer cells need to be able to survive, and we found a way to turn it off," said Dr. White.

The next step, he said, would be ascertaining in rodents whether 6-aminopyrazolopyrimidine can permeate tumors, "hit the target and be effective." If the compound continues to demonstrate efficacy, researchers would begin work to develop a drug with the compound's properties for further testing.

The compound appears to migrate into all tissues of studied mice, but the UT Southwestern researchers don't know yet if it will penetrate solid tumors in the animal, "which is an incredibly important step in evaluating chemicals as drug leads," Dr. White said.

"We've illuminated the dark matter of regulation of an incredibly important oncogenic survival pathway. We've found a new regulatory arm of this pathway, and we've discovered you can inhibit it pharmacologically. That's target validation. The next step is to translate that target validation into development of a medicine," he said.

Other UT Southwestern researchers involved in the study were lead author Yi-Hung Ou, graduate student in cancer biology; Michael Torres and Rosalyn Ram, student research assistants in cancer biology; Dr. Tzuling Cheng, postdoctoral researcher in pediatrics; Dr. Christina Roland, surgery resident; and Dr. Rolf Brekken, associate professor of surgery and pharmacology. Researchers from Hybrigenics of Paris and Amgen Inc. of Thousand Oaks, Calif., also participated.

The work was supported by the National Institutes of Health and the Welch Foundation.


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. Yi-Hung Ou, Michael Torres, Rosalyn Ram, Etienne Formstecher, Christina Roland, Tzuling Cheng, Rolf Brekken, Ryan Wurz, Andrew Tasker, Tony Polverino. TBK1 Directly Engages Akt/PKB Survival Signaling to Support Oncogenic Transformation. Molecular Cell, 2011; 41 (4): 458 DOI: 10.1016/j.molcel.2011.01.019

Cite This Page:

UT Southwestern Medical Center. "Synthetic compound may lead to drugs to fight pancreatic, lung cancer." ScienceDaily. ScienceDaily, 10 March 2011. <www.sciencedaily.com/releases/2011/03/110309162127.htm>.
UT Southwestern Medical Center. (2011, March 10). Synthetic compound may lead to drugs to fight pancreatic, lung cancer. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2011/03/110309162127.htm
UT Southwestern Medical Center. "Synthetic compound may lead to drugs to fight pancreatic, lung cancer." ScienceDaily. www.sciencedaily.com/releases/2011/03/110309162127.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How Nigeria Beat Its Ebola Outbreak

How Nigeria Beat Its Ebola Outbreak

Newsy (Oct. 20, 2014) The World Health Organization has declared Nigeria free of Ebola. Health experts credit a bit of luck and the government's initial response. Video provided by Newsy
Powered by NewsLook.com
Another Study Suggests Viagra Is Good For The Heart

Another Study Suggests Viagra Is Good For The Heart

Newsy (Oct. 20, 2014) An ingredient in erectile-dysfunction medications such as Viagra could improve heart function. Perhaps not surprising, given Viagra's history. Video provided by Newsy
Powered by NewsLook.com
Ebola Worries End for Dozens on U.S. Watch Lists

Ebola Worries End for Dozens on U.S. Watch Lists

Reuters - US Online Video (Oct. 20, 2014) Forty-three people who had contact with Thomas Eric Duncan, the first person diagnosed with Ebola in the U.S., were cleared overnight of twice-daily monitoring after 21 days of showing no symptoms. Rough Cut (no reporter narration). Video provided by Reuters
Powered by NewsLook.com
Beijing Marathon Runners Brave Hazardous Air Pollution

Beijing Marathon Runners Brave Hazardous Air Pollution

AFP (Oct. 19, 2014) Tens of thousands of runners battled thick smog at the Beijing Marathon on Sunday, with some donning masks as the levels of PM2.5 small pollutant particles soared to 16 times the maximum recommended level. Duration: 00:54 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