PCSK9 as a New Player in Cancer: New Opportunity or Red Herring?

Initially described as a factor involved in liver regeneration and neuronal differentiation, proprotein convertase subtilisin/kexin type 9 (PCSK9) has become one of the key regulators of low-density lipoprotein cholesterol. Beside that, a number of studies have suggested PCSK9 may play a role in cancer biology. This is particularly true for gastroenteric (gastric and liver cancers) and lung cancers, where higher PCSK9 levels were associated with the increased ability of the tumor to develop and give metastasis as well as with reduced overall survival. Accordingly, monoclonal antibodies blocking PCSK9 were recently shown to synergize with immunotherapy in different types of cancers to achieve tumor growth suppression through an increased intratumoral infiltration of cytotoxic T cells. Anti-PCSK9 vaccines have been tested in animal models with encouraging results only in colon carcinoma. As most of this evidence is based on pre-clinical studies, this has led to some controversies and inconsistencies, thus suggesting that additional research is needed to clarify the topic. Finally, modulation of intracellular PCSK9 levels by silencing RNA (siRNA) may help understand the physiological and pathological mechanisms of PCSK9.

Automated summary

PCSK9, initially known for its role in liver regeneration and neuronal differentiation, has emerged as a key regulator of low-density lipoprotein cholesterol. Recent studies have shown that PCSK9 may also play a role in cancer biology, particularly in gastroenteric and lung cancers. Higher levels of PCSK9 were associated with increased tumor development, metastasis, and reduced overall survival. Monoclonal antibodies blocking PCSK9 have shown promising results in combination with immunotherapy in suppressing tumor growth. However, more research is needed to fully understand the role of PCSK9 in cancer.