Title:PCSK9 as a New Player in Cancer: New Opportunity or Red Herring?
Volume: 29
Issue: 6
关键词:
PCSK9、癌症、胆固醇、免疫疗法、疫苗、疗法
摘要: 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.
