To examine the impact of TLR2, -4, and -9 expression and activation in pancreatic cancer cells, effects of TLR agonists CpG oligonucleotides 2006 (ODN, TLR9 specific), lipoteichnic acid of Staphylococcus aureus (LTA, TLR2 specific), lipopolysaccharide (LPS, TLR4 specific), and HMGB1 (non-specific) on growth factor expression, tumor cell signaling and cancer proliferation were analyzed to elucidate the potential of TLR signaling as a target for therapeutic strategies in PDAC. This evidence concerns the gene HMGB1 and cancer.