Mucus Production Program Drives Pancreatic Cancer Progression

A recent study reveals that a mucus production program, regulated by the transcription factor SPDEF, is key in promoting the classical subtype of pancreatic ductal adenocarcinoma (PDA). This subtype, associated with higher mucus production, relies on SPDEF to maintain its differentiated state and support tumor growth. SPDEF activates target genes, such as AGR2 and ERN2/IRE1β, which are crucial for mucus production. Disrupting this program not only impairs tumor growth but also promotes a shift from classical to basal-like cell states, underscoring mucus production as a therapeutic vulnerability in PDA.