The discovery of lapatinib (GW572016).

摘要

In the mid-1980s, it was recognized that overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor-2 (HER2) adversely affected the prognosis of some cancer patients. Because EGFR and HER2 are key regulators of cell growth, differentiation, and survival, it was believed that inhibition of these receptors would block downstream signaling and would be antiproliferative. Indeed, by the late 1980s, researchers were creating some of the first targeted inhibitors of tyrosine kinase activity. It was in this context that we began our efforts to develop potential disease therapies using a small-molecule approach to selectively target EGFR and HER2.