Abstract B094: Pentraxin 3 promotes the therapy resistance to sorafenib via regulating apoptosis in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is prevalently regarded as an inflammation-related cancer, characterized by persistent inflammation throughout the tumor microenvironment (TME). Currently, Sorafenib is the first-line targeted therapy drug used for advanced HCC patients. Unfortunately, many patients still face the risk of drug resistance after treatment with sorafenib. Pentraxin 3 (PTX3) has been reported as a secretory protein involved in cancer-related inflammation. It has been found to be overexpressed and acts as an unfavorable prognostic factor in the progression of chronic inflammation-related cancers. A recent study indicated that HCC patients who received sorafenib treatment had significantly higher PTX3 expression. However, the detailed role of PTX3 in these sorafenib-treated HCC patients still remains unclear. Therefore, it is intriguing whether elevated PTX3 contributes to sorafenib resistance in HCC patients. In this study, we observed that PTX3 is responsive to sorafenib, and there is a positive correlation between PTX3 expression and sorafenib resistance. Depletion of PTX3 led to increased sensitivity of HCC cells to sorafenib. For the underlying mechanism, sorafenib-induced PTX3 was found to promote resistance by regulating the anti-apoptotic protein MCL-1 and the pro-apoptotic protein BAX. In vivo experiments also revealed that combined treatment of sorafenib and a PTX3 inhibitor significantly reduced the size of HCC tumors, demonstrating that blocking elevated PTX3 increases sensitivity to sorafenib. Overall, targeting PTX3 attenuates resistance to sorafenib through the regulation of apoptosis, providing a novel therapeutic strategy to enhance therapeutic efficacy in HCC patients undergoing sorafenib treatment.

Citation Format: Ping-Wen Chen. Pentraxin 3 promotes the therapy resistance to sorafenib via regulating apoptosis in hepatocellular carcinoma [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr B094.