Abstract 2333: Verteporfin demonstrates antitumoral effect in murine cholangiocarcinoma models

Abstract

Abstract Cholangiocarcinoma (CCA) is a heterogenous malignancy that is derived from the biliary epithelium. There is growing concern as CCA incidence in United States has steadily increased. Additionally, CCA disproportionately affects different populations, and overall prognosis remains poor with a 5-year survival rate of 10%. Moreover, the Hippo/yes-associated protein (YAP) pathway has been reported to affect various aspects of tumorigenesis and recent reports showed that higher expression of YAP is negatively associated with the survival rate in CCA patients. Thus, we investigated the antitumoral effect of verteporfin, a YAP pathway inhibitor, in YAP/Akt and Notch/Akt hydrodynamic tail vein injected murine models. Our results demonstrated reduced liver weight in verteporfin treated groups compared to the vehicle treated group. Single cell RNA sequence analysis noted the verteporfin treated group had reduced stemness-related expressing cells in the malignant cell population. Furthermore, B cell, CD8+ T cell, and Tumor-Associated Macrophages M1 (TAM M1) populations increased following verteporfin treatment. In summary, this study indicates that verteporfin reduces tumorigenesis in CCA by the regulation of cancer stemness and modulation of immune cells, which includes anti-tumoral/pro-inflammatory TAM M1 in CCA animal models. Citation Format: Jihye Lee, Xin Wang, Jing Bian, Maggie Cam, Changqing Xie. Verteporfin demonstrates antitumoral effect in murine cholangiocarcinoma models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2333.