Scientists have identified the genetic switch GATA6 that determines whether pancreatic cancer cells resist or respond to chemotherapy. The GATA6 gene keeps tumors in a more structured and treatable form. An overactive KRAS-driven pathway shuts down GATA6. When the researchers blocked this pathway, GATA6 levels increased and the cancer cells became more sensitive to chemotherapy. The discovery could help turn some of the most difficult pancreatic tumors into ones that doctors can better control. GATA6 expression distinguishes chemoresistant basal subtypes from classical forms of pancreatic ductal adenocarcinoma. In the COMPASS study, patients with basal-like tumors progressed in 60% of cases treated with modified FOLFIRINOX versus 15% in classic PDAC (P=0.0002). Median overall survival was 9.3 months for classic PDAC versus 5.9 months for basal-like (HR 0.47; P=0.0001).[1][2]