Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance

• Published in: Journal of hematology and oncology Vol. 15; no. 1; pp. 173 - 32
• Main Authors: Fu, Kai, Xie, Fachao, Wang, Fang, Fu, Liwu
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 08.12.2022; BioMed Central; BMC
• Subjects: Binding sites; Cancer; Cancer therapies; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Care and treatment; Chemotherapy; Clinical trials; Drug Resistance, Neoplasm; EGFR-TKIs; Epidermal growth factor; Epidermal growth factor receptors; ErbB Receptors - genetics; Etiology; Genetic aspects; Health aspects; Hematology; Humans; Kinases; Ligands; Lung cancer; Lung cancer, Non-small cell; Lung cancer, Small cell; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Metastases; Mutation; Non-small cell lung carcinoma; NSCLC; Oncology; Osimertinib; Protein-tyrosine kinase receptors; Resistance mechanisms; Review; Small cell lung carcinoma; Targeted cancer therapy; Targeted therapy; Therapeutic strategy; Tyrosine; Chemotherapy; NSCLC; Targeted therapy; Immunotherapy; EGFR-TKIs; Precise medicine; Osimertinib; Therapeutic strategy; Resistance mechanisms
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-022-01391-4

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the preferential options for advanced non-small cell lung cancer (NSCLC) patients harboring EGFR mutations. Osimertinib is a potent irreversible third-generation EGFR-TKI targeting EGFR mutations but has little effect on wild-type EGFR. In view of its remarkable efficacy and manageable safety, osimertinib was recommended as the standard first-line treatment for advanced or metastatic NSCLC patients with EGFR mutations. However, as the other EGFR-TKIs, osimertinib will inevitably develop acquired resistance, which limits its efficacy on the treatment of EGFR-mutated NSCLC patients. The etiology of triggering osimertinib resistance is complex including EGFR-dependent and EGFR-independent pathways, and different therapeutic strategies for the NSCLC patients with osimertinib resistance have been developed. Herein, we comprehensively summarized the resistance mechanisms of osimertinib and discuss in detail the potential therapeutic strategies for EGFR-mutated NSCLC patients suffering osimertinib resistance for the sake of the improvement of survival and further achievement of precise medicine.