MTHFD2 inhibition for UQCR110-deficient ovarian cancer

Inhibiting the mitochondrial enzyme MTHFD2 could help treat ovarian cancers deficient in UQCR11, an electron transport chain subunit that is an MTHF2 paralog.

Bioinformatic analysis of data from The Cancer Genome Atlas identified UQCR11 as a commonly deleted gene in ovarian cancer, and machine-learning based metabolic flux analysis identified MTHFD2 as a synthetic lethal target for UQCR11-deficient cancers, meaning the cell can tolerate deficiency in one of the two proteins, but not both. Higher MTHFD2 expression was associated with lower progression-free survival in ovarian cancer patients with UQCR11 deletions, but not in patients without the deletion...