Targeting the EGFR signaling pathway in cancer therapy: What's new in 2023?

IntroductionEpidermal growth factor receptor (EGFR) is frequently amplified, overexpressed, and mutated in multiple cancers. In normal cell physiology, EGFR signaling controls cellular differentiation, proliferation, growth, and survival. During tumorigenesis, mutations in EGFR lead to increased kinase activity supporting survival, uncontrolled proliferation, and migratory functions of cancer cells. Molecular agents targeting the EGFR pathway have been discovered, and their efficacy has been demonstrated in clinical trials. To date, 14 EGFR-targeted agents have been approved for cancer treatments.Areas coveredThis review describes the newly identified pathways in EGFR signaling, the evolution of novel EGFR-acquired and innate resistance mechanisms, mutations, and adverse side effects of EGFR signaling inhibitors. Subsequently, the latest EGFR/panEGFR inhibitors in preclinical and clinical studies have been summarized. Finally, the consequences of combining immune checkpoint inhibitors and EGFR inhibitors have also been discussed.Expert opinionAs new mutations are threatened against EGFR-tyrosine kinase inhibitors (TKIs), we suggest the development of new compounds targeting specific mutations without inducing new mutations. We discuss potential future research on developing EGFR-TKIs specific for exact allosteric sites to overcome acquired resistance and reduce adverse events. The rising trend of EGFR inhibitors in the pharma market and their economic impact on real-world clinical practice are discussed.

Automated summary

This review discusses the importance of epidermal growth factor receptor (EGFR) in multiple cancers and its role in cellular processes. It also highlights the newly identified pathways, resistance mechanisms, and adverse effects of EGFR inhibitors. The latest research on EGFR/panEGFR inhibitors and the potential of combining them with immune checkpoint inhibitors are summarized. Suggestions for developing specific compounds to target mutations and reducing adverse events are provided.