Epidermal Growth Factor Receptors Unveiled: A Comprehensive Survey on Mutations, Clinical Insights of Global Inhibitors, and Emergence of Heterocyclic Derivatives as EGFR Inhibitors.

Mutations that overexpress the epidermal growth factor receptor (EGFR) are linked to cancers like breast (15-20%), head and neck (10-15%), colorectal (5-8%), and non-small cell lung cancer (10-50%), especially in East Asian populations. EGFR activation stimulates "RAS/RAF/MEK/ERK, PI3K/Akt, and MAPK" pathways, which enhance cell division, survival, angiogenesis, and tumor growth while inhibiting apoptosis and metastasis. Secondary mutations (e.g., "T790M", "C797S"), off-target effects, and resistance due to alternate pathway activation reduce the efficacy of currently available EGFR inhibitors. To address these issues, "novel heterocyclic inhibitors with structural versatility were developed to improve selectivity and binding affinity for mutant EGFR forms. These new EGFR reduce side effects, enhance pharmacokinetics, and enhance therapeutic efficacy at low concentrations. This review focuses on "EGFR mutations in various cancers" detailing the biochemical effects, clinical profiles, and binding interactions of globally approved EGFR inhibitors. Furthermore, it focuses into recent progress in nano-formulations and the development of heterocyclic derivatives that can successfully "target mutant EGFRs" through varied synthesis methods. These inhibitors have the potential to have better binding affinities, selectivity's, and less side-effect. Further research required to refine the structures and develop nanoformulations of EGFR-targeted therapeutics in order to improve therapeutic efficiency and, provide more effective cancer treatments.