In the present study, we sought to determine the therapeutic potential of a MEK inhibitor, namely PD901, either alone or in combination with the pan-mTOR inhibitor MLN0128 for the treatment of K-Ras wild-type CCA in vitro using human CCA cell lines, and in vivo using AKT/YapS127A CCA mice. The gene discussed is MTOR; the disease is cholangiocarcinoma.