Inhibiting PCSK9 for breast cancer metastasis

Inhibiting PCSK9, an enzyme that regulates cholesterol metabolism by degrading lipoprotein receptors, could decrease metastatic initiation and proliferation by stabilizing the lipoprotein receptor LRP1 on tumor cells, whose downstream signaling suppresses expression of metastasis-promoting genes.

Genome-wide association studies of breast cancer patients identified a common gain-of-function missense germline variant in PCSK9 (V474I) that, when homozygous, was associated with shorter overall survival, and conferred a 22% risk of distant metastatic relapse at 15 years, while heterozygous patients had a 2% risk. ...