CDK4/6 inhibitors upregulate cIAP1/2, and Smac mimetic LCL161 enhances their antitumor effects in cholangiocarcinoma cells.

ABSTRACT: Cholangiocarcinoma (CCA) is a highly aggressive bile duct cancer with a poor prognosis and high mortality rates, primarily due to the lack of early diagnosis and effective treatments. We have shown that cyclin D and CDK4/6, key regulators of cell cycle progression, are highly expressed in CCA patients. Moreover, high levels of cyclin D, CDK4, and CDK6 are associated with shorter survival in CCA patients, suggesting that cyclin D and CDK4/6 might be potential targets for CCA therapy. However, we have demonstrated that CDK4/6 inhibitor palbociclib monotherapy is less effective in CCA cells. We have identified Cellular Inhibitor of Apoptosis Proteins 1 and 2 (cIAP1/2), NF-κB target genes that their expression is associated with shorter survival in CCA patients, as potential key regulators of

SUBMITTER: Menapree P 

PROVIDER: S-EPMC11861974 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature