Colon Cancer Drug Discovery Enhanced by New Approach

by Kathy Jones on  November 22, 2010 at 9:30 PM Cancer News
RSS Email Print This Page Comment
Font : A-A+

An old pinworm medicine to be a new lead in the search for compounds that block a signalling pathway implicated in colon cancer has been discovered by scientists.

The findings have suggested a fresh approach for developing therapeutics that target the pathway.
 Colon Cancer Drug Discovery Enhanced by New Approach
Colon Cancer Drug Discovery Enhanced by New Approach

More than 90 percent of sporadic (non-inherited) colon cancers are caused by mutations that result in inappropriate activation of the Wnt (pronounced "wint") signaling pathway.

Blocking this pathway has been a desirable therapeutic target, but its complexity has made it difficult to determine which molecular participants to inhibit.

"There's no obvious target in the pathway where we could say, 'OK, if we inhibit the activity of this protein, that will inhibit Wnt signaling,'" said Ethan Lee, senior investigator of the current study.

To explore Wnt signalling at a biochemical level, Lee and his team developed frog embryo extracts and showed that this cell-free system retained many events of the Wnt signalling pathway.

Using this system, they established a screening strategy to search for chemicals that modify Wnt signalling - with the goal of learning more about the biology of the pathway.

The investigators screened several thousand chemical compounds, from a "library" of FDA-approved drugs and other bioactive compounds. hey found that pyrvinium, an FDA-approved anti-parasite drug, blocked Wnt signaling in the frog extracts.

They tested pyrvinium in cultured cells and in multiple animal models of early development (frogs, nematode worms, fruit flies) and demonstrated that in each case, pyrvinium blocked Wnt signaling.

They also found that in cultured colon cancer cells, pyrvinium inhibited both Wnt signaling and cell proliferation.

To identify the target of pyrvinium, Lee and his colleagues combined four isolated proteins, all with known roles in the Wnt pathway. They found that pyrvinium increased the activity of one of the proteins, an enzyme called casein kinase 1alpha (CK1alpha).

"The targeted cancer therapies that are being intensively studied right now are mostly kinase inhibitors. It's intriguing to think that maybe there are certain kinases - like CK1alpha - that we can activate as targets for treating cancer," said Lee.

The frog embryo extract and screening strategy may also be applied to identifying compounds that modify other developmentally important signaling pathways, added Lee.

The findings were reported in the journal Nature Chemical Biology.

Source: ANI

Post your Comments

Comments should be on the topic and should not be abusive. The editorial team reserves the right to review and moderate the comments posted on the site.
* Your comment can be maximum of 2500 characters
Notify me when reply is posted
I agree to the terms and conditions

More News on:

Drug Toxicity Clinical Trials Cancer and Homeopathy Clinical Trials - The Past and The Future Clinical Trials - Different Phases of the trial Colo-rectal cancer - Management Colorectal Cancer Signature Drug Toxicity Cancer Facts Cancer 

News A - Z


News Search

Medindia Newsletters

Subscribe to our Free Newsletters!

Terms & Conditions and Privacy Policy.

Stay Connected

  • Available on the Android Market
  • Available on the App Store


News Category

News Archive