Clinical Application of PCSK9 Inhibitor in Tumor Therapy

Abstract

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), a key protein secreted by the liver, initially emerged as a research focus in the cardiovascular field due to its central role in regulating lipid metabolism. With the deepening of research, the functional scope of PCSK9 and its inhibitors has continued to expand. They not only demonstrate remarkable efficacy in lipid management and the prevention/treatment of atherosclerotic cardiovascular disease (ASCVD) but also show enormous potential value in cancer prevention and control. Beyond indirectly regulating tumor progression by modulating lipid and inflammatory metabolism, PCSK9 may also exert direct effects on tumorigenesis and progression by participating in tumor cell proliferation, apoptosis signaling pathways, and immune regulation (e.g., influencing the expression of LDLR-related molecules on the surface of immune cells). However, no unified consensus has been reached in existing mechanistic studies. Regarding clinical evidence, there is heterogeneity among the results of multiple cohort studies and clinical trials. Some studies indicate that PCSK9 inhibitors do not significantly increase cancer risk or cancer-related mortality, and even some data suggest potential protective effects against specific types of tumors. Conversely, a small number of studies imply that long-term use may be associated with a slight elevation in the risk of certain cancers. Such discrepancies may stem from heterogeneity in sample size, follow-up duration, tumor types, and baseline characteristics of the study populations. Based on a review of numerous relevant studies, this article concludes that PCSK9 inhibitors may become a key therapeutic agent for cancer treatment in the future.