EGFR mutation mediates resistance to EGFR tyrosine kinase inhibitors in NSCLC: From molecular mechanisms to clinical research

Abstract

With the development of precision medicine, molecular targeted therapy has been widely used in the field of cancer, especially in non-small-cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) is a well-recognized and effective target for NSCLC therapies, targeted EGFR therapy with EGFR-tyrosine kinase inhibitors (EGFR-TKIs) has achieved ideal clinical efficacy in recent years. Unfortunately, resistance to EGFR-TKIs inevitably occurs due to various mechanisms after a period of therapy. EGFR mutations, such as T790M and C797S, are the most common mechanism of EGFR-TKI resistance. Here, we discuss the mechanisms of EGFR-TKIs resistance induced by secondary EGFR mutations, highlight the development of targeted drugs to overcome EGFR mutation-mediated resistance, and predict the promising directions for development of novel candidates.

Keywords: Alflutinib (PubChem CID: 118861389); Almonertinib (PubChem CID: 121280087); EAI045 (PubChem CID: 121231412); EGFR mutations; EGFR-TKI resistance; Future development; JBJ-04-125-02 (PubChem CID: 124173751); JND3229 (PubChem CID: 137628688); NSCLC; Osimertinib (PubChem CID: 71496458); Overcoming drug resistance; Poziotinib (PubChem CID: 25127713); TAK-788 (PubChem CID: 118607832); TAS6417 (PubChem CID: 117918742); TQB3804 (PubChem CID: 138911391).