ErbB Signaling Pathway

The ErbB receptor tyrosine kinase family consists of four cell membrane receptors that are activated following ligand binding and receptor dimerization. Dimerization is a critical step in ErbB family-mediated signaling, and ErbB receptors are able to homodimerize or heterodimerize with other family members depending on the ligand specificity, allowing for multiple receptor combinations. The ErbB receptors signal through many pathways, including the Akt and MAPK pathways, to regulate the cellular processes of proliferation, differentiation, apoptosis, and migration and motility. In addition to functioning on the cell surface, ErbB family proteins are also present in the nucleus where they act both as kinases and transcriptional regulators. Insufficient ErbB signaling is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease. Additionally, several types of cancer are associated with the mutation or increased expression of members of the ErbB family including lung, breast, stomach, colorectal, head and neck, and pancreatic cancers. Because ErbB family members are critical factors in the development and malignancy of these tumors, they have been important therapeutic targets. Unfortunately, cancers treated with current targeted drugs eventually become resistant to them. Thus, the role of combinations of targeted drugs or targeted drugs with cytotoxic therapies instead of single therapeutics are currently being explored.