Hitting the epidermal growth factor receptor (EGFR) both high and low with a combination of drugs for targeted cancer therapy curbs cancer cell growth more effectively than using the drugs each by themselves, researchers from the University of Wisconsin-Madison reported in the August 1 issue of the journal Cancer Research.

EGFR drives unregulated growth in many types of cancer, and the new molecular cancer drugs, cetuximab (Erbitux, ImClone), and gefitinib (Iressa, AstraZeneca) have recently gained FDA approval as therapeutics targeted at the EGFR to inhibit cancer cell proliferation. A third EGFR inhibiting drug, and erlotinib (Tarceva, Genentech), may have FDA approval within a year.

The Wisconsin study examined the combined effect of Erbitux with either Iressa or Tarceva to control growth of head and neck, prostate, and lung cancer cell lines grown in culture, and lung cancer tumors developing in animals.

Tandem application of either Erbitux and Iressa, or Erbitux and Tarceva, proved synergistically more effective than single drug treaent at several levels.

"The combination of Erbitux with either Iressa or Tarceva inhibited cancer cell growth both in cell culture and in live animals more effectively than any of the drugs alone," said the study's senior author, Paul Harari, M.D., associate professor of human oncology, University of Wisconsin Medical School and Comprehensive Cancer Center.

"The impact of these drugs in combination exceeded the effect each had on controlling the growth, cellular signaling, and tumor development when administered alone," added Shyhmin Huang, Ph.D., a senior scientist in Harari's laboratory and lead author on the publication.

The anti-EGFR drugs are of two types:

• The monoclonal antibody Erbitux hits the EGFR high, binding to a specific site on the receptor outside the cell membrane. Erbitux blocks the receptor from responding to extracellular signals that tu
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Contact: Russell Vanderboom, PhD
vanderboom@aacr.org
215-440-9300
American Association for Cancer Research
1-Aug-2004


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