Orphan Cytochromes P450 as Possible Pharmacological Targets or Biomarkers in Breast Cancer.

Although significant advances in the treatment of breast cancer have been made over the last few decades, searching for more effective prophylaxis and therapy for this type of cancer is still topical. Orphan cytochromes (CYPs) P450 are 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/treatment target or biomarker. Of particular interest is CYP4Z1, which seems to be specific for breast cancer, including triple-negative breast cancer (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, exhibit significantly higher expression in breast tumors compared to normal tissues. The available data indicate that these CYP isoforms catalyze the hydroxylation of fatty acids. Their products, such as epoxyeicosatrienoic acids (EETs) or hydroxyeicosatetraenoic acids (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 in prophylaxis. This review summarizes current knowledge of orphan CYPs in breast tissue and their possible application in drug targeting or prognosis assessment.