Epidermal growth factor receptor (EGFR) inhibitor for oncology: Discovery and Development of Erlotinib

This chapter describes epidermal growth factor receptor (EGFR) as a cancer target. and the process of development of erlotinib. Preclinical data supporting erlotinib's advancement into the clinic are also presented in the chapter. Molecular-targeted drug therapies are based upon the understanding of tumor-cell biology to identify oncogenic targets and develop therapeutic approaches to these targets using small-molecular-weight inhibitors, antibodies, and antisense. Erlotinib is a potent inhibitor of purified EGFR tyrosine kinase activity with an IC50 of 2 nM. In responsive tumor cells, erlotinib is shown to block cell-cycle progression at the G1 phase. Erlotinib-induced G1 arrest of some tumors suggests that the sequence of addition of erlotinib and a chemotherapeutic agent determines the efficacy of a combination. Three Phase II single-agent studies with erlotinib on non small–cell lung cancer ( NSCLC), head and neck, and ovarian cancer patients showed that erlotinib was well tolerated and demonstrated patient responses in a number of different types of cancers. It is suggested that understanding the tumor variables of erlotinib responsiveness helps to identify patients who would best respond to treatment, provide for the rational selection of combination agents, and improve administration of combinations whether through sequencing or scheduling of treatments.