MerTK inhibition by UNC569 triggers DNA damage and JNK/p38 MAPK cascade-driven apoptosis in pancreatic cancer

• UNC569 suppresses PDAC cell proliferation, clonogenic growth, migration, and invasion by attenuating epithelial-mesenchymal transition. • UNC569 enhances the sensitivity of PDAC cells to Gemcitabine and promotes apoptosis. • Mechanistically, UNC569 induces DNA damage-mediated G2/M phase arrest and activates JNK/p38 MAPK-dependent apoptotic signaling. • MerTK is established as a promising therapeutic target in PDAC, with UNC569 as a dual-pathway inhibitor.