Provided herein are methods of treating pancreatic ductal adenocarcinoma in a mammalian subject. In some examples, such methods include administering a therapeutically effective amount of a VDR agonist (such as calcipotriol and/or paricalcitol) and administering a therapeutically effective amount of one or more chemotherapeutic agents, wherein the one or more chemotherapeutic agents comprise gemcitabine, 5-fluorouracil, cisplatin, protein-bound paclitaxel, and a PD-1 monoclonal antibody and/or PDL-1 monoclonal antibody.