Are Orphan Cytochromes P450 Suitable Targets for Breast Cancer Prevention and Treatment?

Although significant advances in the treatment of breast cancer have been made over the last decades, searching for more effective prophylaxis and therapy for this type of cancer is still topical. Orphan cytochromes (CYPs) P450 are the enzymes whose functions and substrates are not fully known. The overexpression of some orphan CYPs in breast cancer tissue warrants attention as a possible breast cancer prophylaxis or treatment target. Of particular interest is CYP4Z1, which seems to be specific for breast cancer, including TNBC. The currently available data indicate that inhibition of CYP4Z1 breast-specific expression may reduce the growth, progression, angiogenesis, and invasiveness of breast cancer. Although less specific, the other orphan CYPs, such as CYP2W1, CYP2S1, CYP2U1, and CYP4X1, show much higher expression in breast tumors than in normal tissues. The available data indicate that these CYP isoforms catalyze fatty acids hydroxylation. Their products, such as EETs or HETEs, are considered critical modulators of cancer progression. Therefore, inhibition of the expression and activity of these orphan CYPs might be more useful in cancer treatment than prophylaxis. This review summarizes current knowledge of orphan CYPs in the breast tissue and their possible application in drug targeting.