Divergent roles of SPOP and CHD1 in ACSL4 regulation reveal context-dependent vulnerabilities for targeting ferroptosis

Frequent SPOP mutations and recurrent CHD1 deletions define distinct molecular subtypes of PCa with differential responses to anti-androgen therapy. Ferroptosis, an iron-dependent cell death driven by lipid peroxidation, has emerged as a promising anticancer strategy.

Here, we identify SPOP mutations and CHD1 deletion as key genetic determinants of ferroptosis susceptibility in PCa.