Predicting Outcome of Metastatic Colon Cancer

A clinical study has shown the ability of an assay that measures the activity of human epidermal growth factor receptor (EGRF) to predict treatment outcomes for patients with metastatic colon cancer.

The study, conducted at Princess Margaret Hospital (University of Toronto, Canada), demonstrated that the assay, called eTAG, correlated with disease stability or disease progression in 18 patients with metastastic colorectal cancer being treated with erlotinib (Tarceva). Samples of tumor and skin were taken prior to treatment and seven days later. Each sample was tested with three different eTAG assays that measured the activity of human epidermal growth factor receptor (EGRF), the molecular target of erlotinib. Dysregulation, or malfunctioning, of EGF receptors is associated with disease progression in cancer patients. Assays performed on samples after one week of treatment with erlotinib demonstrated that the presence of EGFR dimers correlated with outcome in the seven patients who had stable disease and were responding to the drug. Eleven patients had progressive disease, meaning they were nonresponders to the treatment.

The researchers used three different methods to predict disease stability. Assays that showed a reduction in Her1/Her1 receptor dimerization, or pairing, coupled with assays that showed an increase in Her1/Her2 receptor dimerization, correlated with stable disease with 100% sensitivity and 88.9% specificity. Assays that showed a reduction in Her1 phosphorylation, or activation, in tumor samples showed the same degree of sensitivity and specificity. Assays that showed a reduction of Her1 phosphorylation in skin samples predicted stable disease with 85.7% sensitivity and 100% specificity.

The eTAG system was developed by ViroLogic, Inc. (South San Francisco, CA, USA). The study was presented by clinical research fellow Carol Townsley, M.D., Princess Margaret Hospital, University of Toronto, at the Gastrointestinal Cancers Symposium held in Hollywood (FL, USA) in January 2005.

"We are very encouraged by the results of this pilot study, which reinforce the potential of the eTAG system to provide truly personalized prognostic information,” commented Sharat Singh, Ph.D., chief technical officer of ViroLogic. "These data mirror results from another recent study utilizing our eTAG technology to predict treatment outcomes in patients with breast cancer.”





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