Epidermal growth factor receptor dual-target inhibitors as a novel therapy for cancer: A review

Overexpression of the epidermal growth factor receptor (EGFR) has been linked to several human cancers, including esophageal cancer, pancreatic cancer, anal cancer, breast cancer, and lung cancer, particularly nonsmall cell lung cancer (NSCLC). Therefore, EGFR has emerged as a critical target for treating solid tumors. Many 1st-, 2nd-, 3rd-, and 4th-generation EGFR single-target inhibitors with clinical efficacy have been designed and synthesized in recent years. Drug resistance caused by EGFR mutations has posed a significant challenge to the large-scale clinical application of EGFR single-target inhibitors and the discovery of novel EGFR inhibitors. Therapeutic methods for overcoming multipoint EGFR mutations are still needed in medicine. EGFR dual-target inhibitors are more promising than single-target inhibitors as they have a lower risk of drug resistance, higher efficacy, lower dosage, and fewer adverse events. EGFR dual-target inhibitors have been developed sequentially to date, providing new options for remission in patients with previously untreatable malignancies and laying the groundwork for a future generation of compounds. This paper introduces the EGFR family proteins and their synergistic effects with other anticancer targets, and provides a comprehensive review of the development of EGFR dual-target inhibitors in cancer, as well as the opportunities and challenges associated with those fields.