PD-161570 sensitizes intrahepatic cholangiocarcinoma to AURKA inhibitor MLN8237 by the YY1/AURKA axis and ferroptosis

This is the authors' abstract. We don't add key points for this paper.

Intrahepatic cholangiocarcinoma (ICC) is one of the most malignant tumors of the intrahepatic bile duct. The cell cycle is a fundamental biological process, and aberrant cell cycle progression will promote the infinite division of tumor cells. The cell cycle-related gene Aurora kinase A (AURKA) is essential for the malignant progression of most cancers, including ICC. However, therapeutic agents targeting AURKA have not been approved in clinical trials due to their insufficient efficacy in treating ICC. Here, we found that PD-161570 inhibited the malignant development of ICC by down-regulating the expression of the AURKA pathway. Our research demonstrated that PD-161570 inhibited the transcriptional regulation of AURKA by targeting YY1. Furthermore, we verified that PD-161570 had synergistic therapeutic effects with the AURKA inhibitor MLN8237 in both in vitro and in vivo experiments of ICC cells. This study reveals the mechanism by which PD-161570 sensitizes MLN8237 and provides an efficient combination regimen, which provides an important theoretical basis and potential treatment regimen for ICC.