Gene Amplification of ErbB-2: From Gene to Therapy
Breast cancer remains the second leading cause of cancer-related deaths worldwide. One of the main obstacles for finding a cure for breast cancer is the inherent heterogeneity of the disease. There are three main subtypes which include estrogen and/or progesterone (ER/PR)-positive, epidermal growth factor receptor-2 (ErbB-2/HER2)-positive, and triple negative that lack expression of ER or PR and express wild type levels of ErbB-2. The etiology of breast cancer development termed the tumorigenic process has been closely linked to gene amplification. Several genes have been shown to be amplified in breast cancer including the ErbB-2 gene on chromosome 17q12-21. The amplification of the ErbB-2 gene is a clear and defined indicator of ErbB-2-positive breast cancer development. In this chapter, we will review the classes of genes that are amplified and linked to breast cancer, discuss the significance of the ErbB-2 signaling pathway to breast cancer progression, targeted therapy, and drug resistance.