TLR4 and familial pancreatic carcinoma: TAMs can also directly support chemoresistance by secreting insulin-like growth factors (IGF)-1 and -2 which activate insulin/IGF receptors on pancreatic cancer cells [138], as well as Resistin, which binds to CAP-1 and TLR-4 on tumor cells and promotes gemcitabine resistance via STAT3 signaling [139].