PIK3CA and pancreatic neoplasm: However, a phase II study that included 121 participants with metastatic pancreatic tumors who randomly received gemcitabine, erlotinib (tyrosine kinase inhibitor-TKI), and metformin or gemcitabine, erlotinib, and placebo [204,205] aimed to assess the effects and the safety of concomitantly inhibiting both PI3K and MAPK signaling pathways at the same time as administering chemotherapy, starting from the hypothesis that the inhibition of only one signaling pathway is insufficient for significant results [205].