Potential role of drug metabolizing enzymes in chemotherapy-induced gastrointestinal toxicity and hepatotoxicity

Introduction: Toxicity of chemotherapy drugs is the leading cause of poor therapeutic outcome in many cancer patients. Gastrointestinal (GI) toxicity and hepatotoxicity are among the most common side effects of current chemotherapies. Emerging studies indicate that many chemotherapy-induced toxicities are driven by drug metabolism, but very few reviews summarize the role of drug metabolism in chemotherapy-induced GI toxicity and hepatotoxicity. In this review, we highlighted the importance of drug metabolizing enzymes (DMEs) in chemotherapy toxicity. Areas covered: Our review demonstrated that altered activity of DMEs play important role in chemotherapy-induced GI toxicity and hepatotoxicity. Besides direct changes in catalytic activities, the transcription of DMEs is also affected by inflammation, cell-signaling pathways, and/or by drugs in cancer patients due to the disease etiology. Expert opinion: More studies should focus on how DMEs are altered during chemotherapy treatment, and how such changes affect the metabolism of chemotherapy drug itself. This mutual interaction between chemotherapies and DMEs can lead to excessive exposure of parent drug or toxic metabolites which ultimately cause GI adverse effect.