Cancer chemopreventive potential of epidermal growth factor receptor inhibitors from natural products

Abstract

Receptor tyrosine kinases (RTKs) are cell membrane-anchored receptors that bind to growth factors, cytokines, and hormones for signal transduction and regulate various signaling cascades. Among the diverse RTKs, epidermal growth factor receptor (EGFR) has been suggested to be upstream of major signaling pathways and regarded as a therapeutic target in cancer metastasis, tumorigenesis or drug resistance. The EGFR belongs to the ErbB RTK family and is significantly overexpressed or mutated in various epithelial malignancies. Many anticancer drugs are used to target EGFR (EGFR tyrosine kinase inhibitors, EGFR TKIs) in the clinic, but critical limitations of those drugs persist. Targeted therapies have improved the prognosis and survival of cancer patients. However, large numbers of patients treated with EFGR TKIs acquire drug resistance, for which multiple mechanisms have been suggested. Therefore, there remains an important need to develop antitumor agents targeting EGFR through the use of natural products with high efficacy. A variety of natural products have been investigated to identify novel antitumor agents that could regulate EGFR via different mechanisms. In addition, combination approaches employing natural products and molecular target therapies have been widely discussed. In the present review, we will summarize the critical roles of EGFR in tumor progression and provide a list of natural products that regulate the EGFR signaling pathway. Targeting EGFR signaling using natural products with different mechanisms may effectively overcome EFGR TKI acquired drug resistance and provide an additional strategy in the treatment of cancer.