Under tumor hypoxic conditions, activation of hypoxia-inducible factor (HIF)-1 promotes metabolism, oxidative stress, chemoresistance, and angiogenesis, with high HIF-1α linked to poor OS.168-170 In vitro silencing of HIF-1α under hypoxic conditions increases apoptosis and GEM sensitivity in PDAC cells.171 In immunocompetent PDAC mice, treatment with GEM and the HIF-1α inhibitor, PX-478, decreased tumor growth via induction of CTL-facilitated cell death.172 Furthermore, hypoxia and HIF activation in CAFs increase tumor progression. This evidence concerns the gene HIF1A and neoplasm.