Blocking 7-DHC synthesis for cancer

Inhibiting the synthesis of 7-DHC, an intermediate metabolite of cholesterol biosynthesis — which is generated by the enzyme EBP, and directly inhibits ferroptosis by suppressing phospholipid peroxidation — could help treat cancer by decreasing tumor growth. 

In a human embryonic kidney cell line, a genome-scale CRISPR/Cas9 library screen identified distal cholesterol synthesis as the top gene enrichment pathway that was differentially expressed in cells that were exposed to a ferroptosis inducer and survived compared with cells exposed to vehicle. DHCR7, an enzyme that converts 7-DHC to cholesterol, was the most depleted guide RNA in the ferroptosis-resistant cells, suggesting that increasing cellular 7-DHC concentrations increases resistance to ferroptosis.  ...