Allosteric mutant-selective fourth-generation EGFR inhibitors as an efficient combination therapeutic in the treatment of non-small cell lung carcinoma.
2021
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are preferred treatments for non-small cell lung carcinoma (NSCLC) that have EGFR activating mutations. Although the initial responses to first- to third-generation EGFR-TKIs is impressive, these agents become ineffective because of the rapid emergence of resistance mediated by EGFR mutations (T790M or C797S). Allosteric mutant-selective fourth-generation EGFR inhibitors have emerged as a possible therapeutic option to overcome resistance. These EGFR inhibitors are less effective than earlier EGFR inhibitors when used as a single agent but have a synergistic effect when used as a combinatorial drug with conventional chemo- or immunotherapeutics. Here, we provide a comprehensive overview of the combined therapeutic efficacy of allosteric EGFR inhibitors in the treatment of EGFR-mutant NSCLC.
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