Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Drug metabolism is a biotransformation process of drugs, catalyzed by drug-metabolizing enzymes (DMEs), including phase I DMEs and phase II DMEs. The aberrant expression of DMEs occurs in the different stages of cancer. It can contribute to the development of cancer and lead to individual variations in drug response by affecting the metabolic process of carcinogen and anticancer drugs. Apart from genetic polymorphisms, which we know the most about, current evidence indicates that epigenetic regulation is also central to the expression of DMEs. This review summarizes differentially expressed DMEs in cancer and related epigenetic changes, including DNA methylation, histone modification, and noncoding RNAs. Exploring the epigenetic regulation of differentially expressed DMEs can provide a basis for implementing individualized and rationalized medication. Meanwhile, it can promote the development of new biomarkers and targets for the diagnosis, treatment, and prognosis of cancer. SIGNIFICANCE STATEMENT: This review summarizes the aberrant expression of DMEs in cancer and the related epigenetic regulation of differentially expressed DMEs. Exploring the epigenetic regulatory mechanism of DMEs in cancer can help us to understand the role of DMEs in cancer progression and chemoresistance. Also, it provides a basis for developing new biomarkers and targets for the diagnosis, treatment, and prognosis of cancer.