Advances in targeting epidermal growth factor receptor signaling pathway in mammary cancer

Abstract

Breast cancer is the most common malignancy among women worldwide. The role of epidermal growth factor receptor (EGFR) in many epithelial malignancies has been established, since it is dysregulated, overexpressed or mutated. Its overexpression has been associated with increased aggressiveness and metastatic potential in breast cancer. The well-established interplay between EGFR signaling pathway and estrogen receptors (ERs) as well as major extracellular matrix (ECM) mediators is crucial for regulating basic functional properties of breast cancer cells, including migration, proliferation, adhesion and invasion. EGFR activation leads to endocytosis of the receptor with implications in the regulation of downstream signaling effectors, the modulation of autophagy and cell survival. Therefore, EGFR is considered as a promising therapeutic target in breast cancer. Several anti-EGFR therapies (i.e. monoclonal antibodies and tyrosine kinase inhibitors) have been evaluated both in vitro and in vivo, making their way to clinical trials. However, the response rates of anti-EGFR therapies in the clinical trials is low mainly due to chemoresistance. Novel drug design, phytochemicals and microRNAs (miRNAs) are assessed as new therapeutic approaches against EGFR. The main goal of this review is to highlight the importance of targeting EGFR signaling pathway in terms of its crosstalk with ERs, the involvement of ECM effectors and epigenetics. Moreover, recent insights into the design of specialized delivery systems contributing in the development of novel diagnostic and therapeutic approaches in breast cancer are addressed.

Keywords: Breast cancer; Epidermal growth factor receptor; Estrogen receptors; Extracellular matrix; MicroRNAs.