Development of Dual Inhibitors Targeting Epidermal Growth Factor Receptor in Cancer Therapy

Epidermal growth factor receptor (EGFR) is of great significance in mediating cell signaling transduction and tumorbehaviors. Currently, third-generation inhibitors of EGFR, especiallyosimertinib, are at the clinical frontier for the treatment of EGFR-mutant non-small-cell lung cancer (NSCLC). Regrettably, therapidly developing drug resistance caused by EGFR mutations andthe compensatory mechanism have largely limited their clinicalefficacy. Given the synergistic effect between EGFR and othercompensatory targets during tumorigenesis and tumor development,EGFR dual-target inhibitors are promising for their reduced risk ofdrug resistance, higher efficacy, lower dosage, and fewer adverseevents than those of single-target inhibitors. Hence, we present thesynergistic mechanism underlying the role of EGFR dual-targetinhibitors against drug resistance, their structure-activity relationships, and their therapeutic potential. Most importantly, weemphasize the optimal target combinations and design strategies for EGFR dual-target inhibitors and provide some perspectives on new challenges and future directions in this field.

Automated summary

EGFR dual-target inhibitors play an important role in the treatment of EGFR-mutant non-small-cell lung cancer by reducing drug resistance risk and improving efficacy with fewer adverse effects.