Epigenetic alterations, like EZH2, may adjust resistance to targeted therapies in tumors, particularly in those with unclear genetic resistance mechanisms.43,44 Indeed, similar findings in EGFR mutated lung adenocarcinoma were discovered in SMARCA4/A2 subunits, which played pivotal roles in adjusting the resistance to Osimertinib.45 Besides, SMARCA4 has been identified as a unique factor for tumor maintenance and oncogenicity.46 In our study, compared to the wild type, patients with concurrent SMARCA4/SMARCB1/EZH2 alterations trended toward worse clinical response to HA121-28. This evidence concerns the gene EGFR and lung adenocarcinoma.