A momentous progress update: epidermal growth factor receptor inhibitors as viable agents for combating cancer

Abstract

The epidermal growth factor receptor (EGFR) family comprises four distinct members with similar framework characteristics: EGFR (HER1/ErbB1), ErbB2 (HER2/neu), ErbB3 (HER3), and ErbB4 (HER4). EGFR plays a pivotal role in cellular signaling pathways that regulate key pathological processes, including apoptosis, uncontrolled cell proliferation, metastasis, and angiogenesis. However, clinically used EGFRs such as apatinib, selumetinib, gefitinib, vandetanib, and erlotinib are not selective, thereby resulting in troublesome side effects. Drug obstruction, alteration, and specificity represent a few of the primary obstacles in the development of unique key compounds as EGFR inhibitors, stimulating medicinal chemists to discover innovative chemotypes. The development of drugs that block specific stages of cancerous cells, such as EGFR, is one of the main goals of many cancer treatments, including breast and lung tumors. Thus, the current study endeavored to summarize the numerous recent advancements (2016–2024) in the research and development of diverse epidermal growth factor receptor (EGFR) inhibitors, focusing on pyrrole, indole, pyrimidine, oxadiazole, isoxazole, and other structural classes. Preclinical, clinical, structure–activity relationships (SAR) with mechanism-based and in silico research, and other relevant data are compiled to offer directions for the scientific discovery of novel EGFR inhibitors with conceivable uses in therapy. The research trajectory of this entire field will provide incessant opportunities for the discovery of novel drug molecules with improved efficacy and selectivity.