Shedding Light on Acquired Treatment Resistance in Lung Cancer

NEW YORK APR 26, 2007 (Reuters Health) - New research indicates that lung cancers develop resistance to gefitinib (Iressa) through MET oncogene amplification on ERBB3 signaling.

Gefitinib and erlotinib are used to treat non-small cell lung cancers with activating mutations in the gene for epidermal growth factor receptor. Unfortunately, the overwhelming majority of tumors eventually become resistant to these drugs. In half of the cases, this resistance is due to the emergence of a second mutation in the receptor. The reason for resistance in the remaining half has been unclear.

The findings from the new study, which appear in the April 26th online issue of Sciencexpress, suggest that MET amplification, resulting in activation of ERBB3 signaling, is an important cause of gefitinib resistance.

Moreover, senior author Dr. Pasi A. Janne, from Dana-Farber Cancer Institute in Boston, and colleagues further show that in vitro gefitinib sensitivity can be restored by blocking MET signaling.

MET amplification was apparent in 4 out of the 18 tested tumor samples that had developed resistance to gefinitib or erlotinib.

The authors note that because MET amplification promotes resistance through an ERBB3 pathway, it could be the cause of gefitinib or erlotinib resistance for other ERBB3-driven malignancies, such as glioblastoma multiforme, colorectal cancer, and head and neck cancer.

SOURCE:

• Sciencexpress 2007 online.