( lleagues wanted to determine whether Er...)Two designer drugs hit same lung cancer target, but only one is effective

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.

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Source:Dana-Farber Cancer Institute


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