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1956 up to 2020, and inclusion criteria were original peer-reviewed publications. To date, PCSK9 has been scantly investigated in cancer. The question that needs to be discussed is "How does PCSK9 act in cancer pathophysiology and what are the risks or benefits associated to its inhibition?". We reviewed the available publications highlighting the contribution of this proprotein convertase in pathways related to cancer, with focus on the potential implications of its long-term pharmacological inhibition in cancer therapy. To date, PCSK9