Some patients with nonsmall-cell lung cancer (NSCLC) have mutant versions of the epidermal growth factor receptor (EGFR). This protein activates signaling pathways involved with cell growth and survival. Previous studies have shown that small-molecule EGFR inhibitors such as gefitinib and erlotinib (Tarceva) work by blocking signals in the intracellular domain of EGFR--between the EGFR and the cell nucleus. Additionally, many NSCLC patients with mutations in this intracellular domain of EGFR appear to benefit from these drugs.
Toru Mukohara, M.D., of the Dana-Farber Cancer Institute in Boston, and colleagues decided to examine the effectiveness of another type of drug that targets EGFR--a monoclonal antibody called cetuximab, which is approved for the treatment of metastatic colorectal cancers that overexpress EGFR. Cetuximab targets EGFR by preventing its activation by extracellular signals, or signals occurring outside of the cell, as opposed to the intra-cellular signal blocking of drugs like gefitinib.
The researchers treated seven different NSCLC cell lines with cetuximab or gefitinib, and compared the drugs' effects on cell growth and cell death or apoptosis. They found that both drugs similarly inhibited the growth of the NSCLC cells containing the normal form of EGFR. However, gefitinib was more effective than cetuximab at inhibiting cell growth and increasing apoptosis in NSCLC cells with mutant EGFR.
The authors note that because these studies were carried out in cell lines, and not in humans, issues such as which drug has more toxicity or negative side effects are
Contact: Elana Hayasaka
Journal of the National Cancer Institute