The Role of PI3K Inhibition in Suppressing Pancreatic Cancer Progression: Mechanistic Insights From Copanlisib Studies

Accumulating evidence has demonstrated that the overactivation of phosphoinositide 3-kinase (PI3K) is closely linked to the development and progression of pancreatic cancer, establishing it as a potential therapeutic target. Although several PI3K inhibitors have been developed, few have shown efficacy in treating pancreatic cancer. Consequently, there is an ongoing need for a deeper understanding of the anticancer effects exerted by PI3K inhibitors in this context. In this study, we selected copanlisib, the first marketed PI3K inhibitor, as a research tool to systematically evaluate its antipancreatic cancer effects, with the aim of validating the feasibility of using PI3K inhibitors for the treatment. In vitro studies demonstrated that copanlisib inhibited the proliferation and colony-forming ability of typical pancreatic ductal adenocarcinoma cell lines. Additionally, it induced G2/M phase arrest in pancreatic cancer cells, thereby promoting apoptosis in tumor cells. In in vivo studies, copanlisib treatment effectively inhibited pancreatic cancer growth and reduced Ki-67 expression by suppressing the PI3K signaling pathway in a xenograft mouse model. Collectively, these findings provide preliminary validation for the concept that PI3K inhibitor copanlisib significantly inhibits pancreatic cancer cell proliferation and tumor growth in both in vitro and in vivo settings, promoting apoptosis and suppressing the PI3K signaling pathway, which indicates its potential in pancreatic cancer treatment. We anticipate that these findings will serve as a reference for the clinical application of PI3K inhibitors in managing pancreatic cancer.