Maximizing Lung Cancer Chemotherapy

Most cases of NSCLC are characterized by overactive normal EGFR, while a small percentage displays a mutated form.

Gefitinib inhibits EGFR tyrosine kinase by binding to the adenosine triphosphate (ATP)-binding site of the enzyme. The function of the EGFR tyrosine kinase in activating the Ras signal transduction cascade is inhibited, and malignant cells are repressed.

Cetuximab is a recombinant, human/mouse chimeric monoclonal antibody that binds specifically to the extracellular domain of human EGFR. Cetuximab is composed of the Fv regions of a murine anti-EGFR antibody with human IgG1 heavy and kappa light chain constant regions and has an approximate molecular weight of 152 kDa. Cetuximab is produced in mammalian (murine myeloma) cell culture.


Investigators at the Dana-Farber Cancer Institute (Boston, MA, USA) worked with tissue culture lines of lung cancer cells having either normal (wild-type) or mutant EGFR. The cell cultures were treated with various dilutions of gefitinib or cetuximab and cell growth was monitored. Propidium iodide staining and immunoblotting were used to determine the onset of apoptosis.


Results published in the August 17, 2005, issue of the Journal of the [U.S.] National Cancer Institute revealed that while both drugs were effective against the cells with wild-type EGFR, only gefitinib killed those cells containing mutated 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,” said senior author Dr. Pasi A. Janne, professor of medical oncology at the Dana-Farber Cancer Institute. "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.”





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Dana-Farber Cancer Inst