EGFR Kinase: Potential target for Cancer therapy

Abstract

Receptor tyrosine Kinase (RTK) is the main mediators of the signaling network that transmit extracellular signals into the cell, and control cellular differentiation and proliferation. Tyrosine Kinase inhibitors directed against the epidermal growth factor receptor (EGFR) are the first molecular-targeted agents to be approved in the US and other countries for the treatment of advanced NSCLC after failure of chemotherapy. The EGFR autocrine pathway plays a crucial role in human cancer since it contributes to a number of highly relevant processes in tumor development and progression, including cell proliferation, regulation of apoptotic cell death, angiogenesis and metastatic spread. Among a variety of approaches used to target EGFR signaling, EGFR blocking monoclonal antibodies and small molecular weight EGFR tyrosine Kinase compounds have been successfully developed. The results of a large body of preclinical studies and clinical trials suggest that targeting the EGFR could represent a significant contribution to cancer therapy. Both types of agent exert a significant anti-proliferative activity when used alone or in combination with conventional antitumor treatments, such as chemotherapy or radiation therapy. Recent evidence suggests the role of specific activating mutations within the tyrosine kinase domain of EGFR to explain the dramatic responses to small molecule tyrosine kinase inhibitors in a subgroup of lung cancer patients. However, the intrinsic
molecular mechanisms of resistance to these drugs are still unclear. The aim of present review is on the cellular responses of EGFR and their implications for cancer therapy.