Featured Research

from universities, journals, and other organizations

Drug-target database lets researchers match old drugs to new uses

Date:
May 22, 2014
Source:
University of Colorado Denver
Summary:
There are thousands of drugs that silence many thousands of cancer-causing genetic abnormalities. Some of these drugs are in use now, but many of these drugs are sitting on shelves or could be used beyond the disease for which they were originally approved. Repurposing these drugs depends on matching drugs to targets. A study recently published describes a new database and pattern-matching algorithm that allows researchers to evaluate rational drugs and drug combinations, and also recommends a new drug combination to treat drug-resistant non-small cell lung cancer.

There are thousands of drugs that silence many thousands of cancer-causing genetic abnormalities. Some of these drugs are in use now, but many of these drugs are sitting on shelves or could be used beyond the disease for which they were originally approved. Repurposing these drugs depends on matching drugs to targets.

A study recently published in the journal Bioinformatics describes a new database and pattern-matching algorithm that allows researchers to evaluate rational drugs and drug combinations, and also recommends a new drug combination to treat drug-resistant non-small cell lung cancer.

"Most cancers have more than one genetic alternation. And even genetically targeted drugs tend to affect more than only their stated target. And so the challenge is matching drugs with many effects to cancers with many causes in a way that best maps the drugs' effects onto the intended targets," says Aik Choon Tan, PhD, investigator at the University of Colorado Cancer Center and associate professor of Bioinformatics at the CU School of Medicine.

There are about 500 kinases in the human genome, each of which represents a potentially important drug target. Tan describes the database as a spreadsheet with 500 columns, each column representing a kinase. Heading each row is a drug and then in each column cell is that drug's activity against the kinase.

"Imagine you know a cancer is caused by five kinases acting in unison," Tan says. "Our approach would allow you to query the database for this pattern and discover the drug or combination of drugs that best match the genetic needs."

Because many of these drugs have already earned FDA approval for use in other diseases, the processes of repositioning these drugs for new diseases is much less involved and expensive than if drug developers had started fresh.

Tan and colleagues put the technique to use to recommend drugs that could turn off the kinases that non-small cell lung cancer uses to create resistance existing treatments. It's been an important question -- many lung cancers depend on over-activation of the gene EGFR, but then when EGFR inhibitors like gefitinib or erlotinib are used, the cancers tend to activate other "kinases" that allow the cancer to by-pass around this dependence. Tan and colleagues asked what are these kinases that allow lung cancer to evade gefitinib, and what other drug might turn them off.

The answer may be in the drug bosutinib, developed by Pfizer, which earned FDA approval in 2013 for the treatment of chronic myeloid leukemia. The drug out-competes the body's energy source, ATP, for space in kinases and so keeps them from being activated. And it turns out that bosutinib may inhibit the activity of exactly the kinases that EGFR-dependent lung cancers need to mutate around the challenge of EGFR inhibitors.

In tests on EGFR-dependent lung cancer cell lines, Tan and colleagues show that the drugs gefitinib and bosutinib "showed additive and synergistic effects."

In a mechanism that Tan hopes will become common, his group will now hand off this rational combination to other researchers at the CU Cancer Center and elsewhere who will move the drugs toward a human clinical trial.


Story Source:

The above story is based on materials provided by University of Colorado Denver. The original article was written by Garth Sundem. Note: Materials may be edited for content and length.


Journal Reference:

  1. J. Kim, V. T. Vasu, R. Mishra, K. R. Singleton, M. Yoo, S. M. Leach, E. Farias-Hesson, R. J. Mason, J. Kang, P. Ramamoorthy, J. A. Kern, L. E. Heasley, J. H. Finigan, A. C. Tan. Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy. Bioinformatics, 2014; DOI: 10.1093/bioinformatics/btu323

Cite This Page:

University of Colorado Denver. "Drug-target database lets researchers match old drugs to new uses." ScienceDaily. ScienceDaily, 22 May 2014. <www.sciencedaily.com/releases/2014/05/140522105140.htm>.
University of Colorado Denver. (2014, May 22). Drug-target database lets researchers match old drugs to new uses. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2014/05/140522105140.htm
University of Colorado Denver. "Drug-target database lets researchers match old drugs to new uses." ScienceDaily. www.sciencedaily.com/releases/2014/05/140522105140.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

Ivorians Abandon Monkey Pets in Fear Over Ebola Virus

AFP (Sep. 16, 2014) Since the arrival of Ebola in Ivory Coast, Ivorians have been abandoning their pets, particularly monkeys, in the fear that they may transmit the virus. Duration: 00:47 Video provided by AFP
Powered by NewsLook.com
Study Links Male-Pattern Baldness To Prostate Cancer

Study Links Male-Pattern Baldness To Prostate Cancer

Newsy (Sep. 16, 2014) New findings suggest men with a certain type of baldness at age 45 are 39 percent more likely to develop aggressive prostate cancer. 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