Cytochrome P450: Implications for human breast cancer

Abstract

The treatment options for breast cancer include endocrine therapy, targeted therapy and chemotherapy. However, some patients with triple-negative breast cancer cannot benefit from these methods. Therefore, novel therapeutic targets should be developed. The cytochrome P450 enzyme (CYP) is a crucial metabolic oxidase, which is involved in the metabolism of endogenous and exogenous substances in the human body. Some products undergoing the metabolic pathway of the CYP enzyme, such as hydroxylated polychlorinated biphenyls and 4-chlorobiphenyl, are toxic to humans and are considered to be potential carcinogens. As a class of multi-gene superfamily enzymes, the subtypes of CYPs are selectively expressed in breast cancer tissues, especially in the basal-like type. In addition, CYPs are essential for the activation or inactivation of anticancer drugs. The association between CYP expression and cancer risk, tumorigenesis, progression, metastasis and prognosis has been widely reported in basic and clinical studies. The present review describes the current findings regarding the importance of exploring metabolic pathways of CYPs and gene polymorphisms for the development of vital therapeutic targets for breast cancer.

Keywords: arachidonic acid; breast cancer; cytochrome P450; metabolism.

Figure 1.

Schematic representation of arachidonic acid metabolic pathway via the major CYP enzymes. Metabolites (20-HETE, EETs and PGI₂) possess tumor-promoting effects on breast cancer. 20-HETE, 20-hydroxy-eicosatetraenoic acids; CYP, cytochrome P450; EETs, epoxy-eicosatrienoic acids; HET0016, N-hydroxy-N0-(4-butyl-2 methyl phenyl) formamidine; PGH₂, prostaglandin H₂; PGI₂, prostacyclin.