We then set forth to identify the newly emerging therapeutic targets in CDK4/6 inhibitor-resistant cancer cells by leveraging the acquired vulnerability of the cancer cells that grew under CDK4/6 inhibition in the hope that inhibition of the novel target would synergize with CDK4/6 inhibition and prohibit the escape of CCA from CDK4/6 inhibition. This evidence concerns the gene CDK4 and cholangiocarcinoma.