HES1 and lung adenocarcinoma: In EGFR-mutant lung adenocarcinoma, elevated levels of Hes1 protein are associated with shorter progression-free survival in patients treated with tyrosine kinase inhibitors (TKIs); however, the combination of Notch inhibitors with TKIs (such as gefitinib and osimertinib) significantly reduces Hes1 expression and overcomes drug resistance (194).