Iressa Shows Promise For Treatment Of Metastatic Breast Cancer When Combined With Hormonal Therapy
These findings are surprising and represent the first positive study for Iressa in breast cancer, as well as for the entire class of drugs known as epidermal growth factor receptor tyrosine kinase inhibitors, ...Read more
Since: Dec 05
#1 May 21, 2008
Epidermal growth factor receptors (EGFR) are typical enzyme-linked receptors, with an exterior ligand that binds with a signaling molecule, and an internal tyrosine kinase enzyme site. Drugs are developed to inhibit expression at either of these sites. Iressa binds to the external ligand, and has shown activity against non-small-cell lung cancer, adenocarcinoma and breast cancer. In the case of breast cancer, Iressa inhibits an overactive HER/neu tyrosine kinase.
Since unregulated signal transduction is a primary characteristic of many types of cancers, researchers are very active in the pursuit of inhibitors that can control the process. These drugs promise to become an essential part of the physician's armament against cancer, particularly those cancers that have developed resistance to other forms of treatment.
However, setbacks with Iressa, that specifically target protein kinases, reflect a lack of validated biomarkers. The next classes of signal transduction inhibitors, the vascular endothelial growth factor receptor (VEGFR) also lack validated biomarkers.
What is needed is to test the concept of targeted cancer drugs with biomarkers as pharmacodynamic endpoints, and with the ability to measure multiple parameters in cellular screens now in hand using flow cytometry.
The importance of mechanistic work around targets as a starting point for drug development should be downplayed in favor of a systems biology (cell function analysis) approach were compounds are first screened in cell-based assays, with mechanistic understanding of the target coming only after validation of its impact on the biology.
The fundamental role of kinases in cancer biology and the success of pioneering therapeutics have prompted intensive efforts to develop kinase inhibitors. However, many of these drugs cry out for validated clinical biomarkers to help set dosage and select people likely to respond.
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