SMAD4 and pachyonychia congenita: However, the clinical response rate is only ≈20%, with overall survival ranging from 6.7 to 10.1 months.[5, 6, 7] The major driver genes of PC include KRAS (90%), TP53 (71%), CDKN2A (24%), and SMAD4 (17%).[8, 9] Although these are well‐established driver genes in PC, their therapeutic potential as clinical drug targets remains limited.[9, 10]Therefore, further elucidation of the key events driving the malignant progression and gemcitabine resistance in PC is of great clinical value.