Epidermal growth factor receptor: mechanisms, networks, and medicines

Abstract This special edition of Philosophical Transactions is linked to a Discussion meeting entitled ‘Epidermal growth factor receptor after 40 years’, held 9–10 December 2024. The meeting was timed to mark the 40th anniversary of the sequencing and cloning of the epidermal growth factor receptor (EGFR) in landmark studies published in 1984. Laboratory and clinical scientists gathered in London to share new information and discuss how the past four decades have seen EGFR progress from a newly discovered driver of human cancer to a key target for numerous cancer therapies that are benefitting many patients. Articles in this special edition chronicle the history of the initial discoveries and how they shaped subsequent progress in understanding and in developing new therapeutics. Halfway through the four decades, in 2004, new activating mutations in EGFR were discovered in lung cancer, bringing gene sequencing to the fore in making clinical decisions. These mutations are discussed in several articles, as are mechanistic views of their impact on EGFR structure, function and inhibitor response. Despite these great advances, we are still only beginning to understand the complexity of EGFR signalling and how to target it in cancer—with many new ideas discussed in this edition. This article is part of the discussion meeting issue ‘Epidermal growth factor receptor after 40 years’.