Allosteric mutant-selective fourth-generation EGFR inhibitors as an efficient combination therapeutic in the treatment of non-small cell lung carcinoma

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) show most preferable treatment for non-small cell lung carcinoma (NSCLC) with EGFR activating mutations. Despite initial impressive response of first-, to third-generation EGFR-TKIs, these agents become ineffective because of rapid emergence of EGFR mutations (T790M or C797S) mediated resistance. Allosteric mutant-selective fourth-generation EGFR inhibitors appeared to be possible therapeutic option to overcome resistance. These EGFR inhibitors are less effective as a single agent but provide synergistic effect as a combinatorial drug with conventional chemo- or immunotherapeutic. Here, we aim to highlight the comprehensive overview on combined therapeutic efficacy of allosteric EGFR inhibitors for the treatment of EGFR mutant NSCLC.