ErbB/Her dimerization profiles and targeted therapy in breast and lung cancer

Abstract

808 Background: Aberrant signaling pathway drives cancer. This is because of the dysregulation of signaling by the erbB family of transmembrane receptor tyrosine kinases. The EGFR family includes human erbB1 (EGFR or Her1), erbB2 (Her2 or neu), erbB3 (Her3), and erbB4 (Her4). The aberrant signaling can be due to various reasons, like for example ligand overproduction, over-expression of the receptors on the cell surface, mutations or defective internalization of the receptor from the cell surface. Whatever the reason, these pathways become active in cancer and it is important to shut them down using appropriate therapy. Employing eTag assays, we can identify the active pathways in each cancer patient in a quantitative manner and provide a dimerization profile for targeted therapy. Materials and Method: We have measured the total Her1, Her2 and Her3 receptor expression levels and Her1/2, Her2/3 Her1/1 and Her2/2 dimerization profiles in 73 breast and 37 lung tissues using the proximity-based multiplexed eTag assays. Results: Our results indicate that the total receptor expression levels are different in different tumor samples. Moreover, the dimerization profiles may or may not correlate with the total receptor expression levels. ErbB/Her dimerization was detected only in tumor tissues but not in normal tissues, whether matched with the same donor or not. We also found that in breast tissues, all tumor samples had higher Her-2 levels compared to normal tissues. These results suggest that targeting therapy based on individual needs is the way to go in the treatment of breast and lung cancer. Conclusion: eTag technology can be a very useful tool in determining the total receptor expression levels and dimerization profiles in individual cancer patients, thereby providing a valuable prognostic tool for stratifying cancer patients for targeted therapy. In addition, eTag technology can also help in monitoring the patient response to targeted therapy during the course of drug treatment. No significant financial relationships to disclose.