Iron is essential for cell growth and replication, but aggressive or metastasized cancers often rely on large iron levels, named an “iron-addiction” status. Contrary to healthy cells which synthesize early precursor, intermediate, and heme end products for survival, cancer cells only require certain genes for accumulation of heme intermediates and end products for survival. This cancer rewiring process is termed “heme overdrive”, which is present in all cancer cells but absent in all normal cells.
USF investigators have disclosed a method of identifying and targeting cancer iron-addiction as an attractive novel approach to exploit cancer metabolic vulnerabilities. They show that inducing the accumulation of heme precursor metabolites followed by treating with a ferroptosis compound, cancer cell death occurs with low to no toxicity in normal cells.
Defining heme overdrive with CRISPR KO-derived essentiality data in over 300 cancer cell lines. Analysis of CRISPR essentiality data enables mapping of heme overdrive in 27 major types of cancer. Color mapping indicates average cancer cell growth dependence revealed by CRISPR KO of a given gene.