Recent advances of novel fourth generation EGFR inhibitors in overcoming C797S mutation of lung cancer therapy.

Lung cancer is the second place among the global cancer population in term of the morbidity and mortality, while non-small cell lung cancer (NSCLC) accounts for the largest proportion of all lung cancer patient. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are commonly used in the treatment of NSCLC. Despite of the success in coping with EGFR kinase resistance lung cancer using the first three generations of EGFR-TK inhibitors (EGFR-TKIs), the new problem of resistance to Osimertinib occurred due to the newly developed EGFR mutation. In recent years, scientists have proposed several pharmacochemical strategies for the treatment of Osimertinib-resistant NSCLC patients. This paper intends to collect the references in this field since 2021 and to summarize the pharmacochemical processes and strategies in discovery of novel EGFR-TKIs for overcoming C797S mutation in lung cancer patients. It could serve as quick information provider for further structural modifications and drug discovery.