Navigation Links
Two designer drugs hit same lung cancer target, but only one is effective

Two designer cancer drugs differed dramatically in a laboratory test comparing their ability to shut down a mutant, overactive growth signal in lung cancer cells, reports a team headed by scientists at the Dana-Farber Cancer Institute.

Although both drugs killed cells containing a normal but overactive EGFR (epidermal growth factor receptor) molecule, only gefitinib (Iressa) killed lung cancer cells containing a mutated EGFR molecule. The monoclonal antibody drug cetuximab (Erbitux) had little effect on the mutant signal, evidently because it strikes at a different part of the EGFR molecule.

Reporting in the Aug. 17 issue of the Journal of the National Cancer Institute, the researchers say that the divergent results add to growing evidence that mutations in the targets of designer drugs critically influence their effectiveness. Erbitux is an effective inhibitor of EGFR signals in colorectal cancer, which involves a normal, not mutant, EGFR molecule.

"We now know of several groups of patients who benefit from therapy targeted at EGFR," says Pasi A. Janne, MD, PhD, of Dana-Farber, and a senior author of the paper. "Those with EGFR mutations will benefit from Iressa or Tarceva (erlotinib), while another group, without EGFR mutations, will benefit from Erbitux."

The lead author is Toru Mukohara, MD, and the senior authors are Bruce E. Johnson, MD, and Jänne, all of Dana-Farber.

Iressa and Erbitux both are designed to squelch the overexpressed, or overactive, EGFR signal that spurs growth in several types of cancer. In some forms of the disease, including lung cancer of the non-small-cell type, and colorectal cancer, the abnormal signals are generated by a normal EGFR molecule. In a small percentage of patients with non-small-cell lung cancer (NSCLC), the overactivity stems from a mutant EGFR protein: those patients tend to have a better outlook, and Iressa and Tarceva are particularly effective for them.

Mukohara and his co lleagues wanted to determine whether Erbitux might be another option for NSCLC patients who carry the EGFR mutation. To test this idea, they treated lung cancer cell lines in the laboratory with Iressa and with Erbitux. They reported that both drugs blocked the excess signals in cells with normal EGFR, but only Iressa was significantly effective in those carrying a mutant EGFR.

"It tells us something about the difference in the drugs' ability to cause a regression of the cancer by shutting down the abnormally active growth signal receptor, EGFR," says Janne. "If you want to choose a way of inhibiting the mutant EGFR receptor, you would pull Iressa and Tarceva off the shelf, not Erbitux."

Iressa and Tarceva are known as small-molecule drugs that can be taken orally and block the part of the EGFR molecule that's located within the cell. In NSCLC, patients with the mutation often respond to both drugs, though only Tarceva has helped patients live slightly longer in clinical trials. Erbitux is a monoclonal antibody drug that binds to a portion of the EGFR receptor that extends outside the cell. This difference in action is the apparent explanation for why they performed differently against the mutant EGFR cells.

The scientists also looked at cases of four NSCLC patients with EGFR mutations who had been treated with the two drugs. The scientists' predictions were confirmed: all patients had some tumor shrinkage when they received Iressa, but none of the cancers responded to Erbitux.

Janne says that the experiment told the scientists something new about the biology of the EGFR mutation in NSCLC. "The lesson is, to inhibit the mutant receptor, you need to inhibit the domain of the EGFR molecule that lies within the cell, as opposed to the extracellular domain," Jänne says.


Source:Dana-Farber Cancer Institute

Related biology news :

1. Mouse with designer liver has enhanced glucose tolerance, insulin response
2. Molecular machine may lead to new drugs to combat human diseases
3. Researchers identify target for cancer drugs
4. MetaChip provides quick, efficient toxicity screening of potential drugs
5. Newly discovered pathway might help in design of cancer drugs
6. UNC launches study of liver injury caused by drugs
7. Findings have implications for tracking disease, drugs at the molecular level
8. Future diabetes drugs may target new protein interaction
9. UCLA study assesses cost-effectiveness of Hepatitis B drugs
10. Sponges as drugs
11. Newest HIV drugs should be used with FUZEON(R)
Post Your Comments:

(Date:11/17/2015)... 2015 Paris , ... --> Paris , qui s,est tenu ... le leader de l,innovation biométrique, a inventé le premier ... empreintes sur la même surface de balayage. Jusqu,ici, deux ... pour les empreintes digitales. Désormais, un seul scanner est ...
(Date:11/12/2015)... 2015  Arxspan has entered into an agreement ... for use of its ArxLab cloud-based suite of ... partnership will support the institute,s efforts to electronically ... information internally and with external collaborators. The ArxLab ... the Institute,s electronic laboratory notebook, compound and assay ...
(Date:11/9/2015)... DUBLIN , Nov. 09, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) ...
Breaking Biology News(10 mins):
(Date:11/27/2015)... November 27, 2015 ... popularity of companion diagnostics is one of ... market with pharmaceutical companies and diagnostic manufacturers ... tests. . --> ... report on global cancer biomarkers market spread ...
(Date:11/25/2015)... , November 26, 2015 ... Biobanking Market 2016 - 2020 report analyzes that ... integrity and quality in long-term samples, minimizing manual ... cost-effectiveness. Automation minimizes manual errors such as mislabeling ... efficiency. Further, it plays a vital role in ...
(Date:11/25/2015)... Studies reveal the differences in species of ... way for more effective treatment for one of the most ... --> --> Gum disease is ... yet relatively little was understood about the bacteria associated with ... by researchers from the WALTHAM Centre for Pet Nutrition together ...
(Date:11/25/2015)... QUEBEC CITY , Nov. 25, 2015 /PRNewswire/ ... "Company"), affirms that its business and prospects remain ... , Zoptrex™ (zoptarelin doxorubicin) recently received DSMB ... program to completion following review of the final ... met Phase 2 Primary Endpoint in men with ...
Breaking Biology Technology: