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Metabolism (Non-CYP Enzymes)

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The fate of xenobiotics, and therefore the efficacy or toxicity of chemotherapeutics, may be dictated by the action of metabolizing enzymes. The metabolism of drugs is categorized into reactions that chemically modify a compound (phase 1) or conjugate a compound with a small reactive biomolecules to yield a polar product amenable to excretion (phase 2). While oxidation by cytochrome P450 enzymes is the primary route of metabolism for many drugs, many additional enzymes may modify the structure and thus function of a wide range of agents. The primary function of these non-CYP enzymes may be detoxification, which may coexist with an endogenous biochemical function. While drug metabolism can lead to a loss of efficacy, there are also numerous commonly used cancer chemotherapeutic agents where metabolism is essential for the generation of the active compound. This review outlines what is known about the metabolism of anticancer drugs by non-CYP enzymes and discusses the potential impact of gene expression and genotypic variation of metabolizing enzymes on efficacy and toxicity.

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Acknowledgments

DJ, SAC, and AVB are supported by Cancer Research UK.

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  1. Northern Institute for Cancer Research, Newcastle University, Paul O’Gorman Building, Medical School, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK

    David Jamieson, Sally A. Coulthard & Alan V. Boddy

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  1. Sidney Kimmel Comprehensive Cancer Cente, Baltimore, Maryland, USA

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  2. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

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  3. Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

    William D. Figg

  4. Moffitt Cancer Center, Tampa, Florida, USA

    Howard L. McLeod

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Jamieson, D., Coulthard, S.A., Boddy, A.V. (2014). Metabolism (Non-CYP Enzymes). In: Rudek, M., Chau, C., Figg, W., McLeod, H. (eds) Handbook of Anticancer Pharmacokinetics and Pharmacodynamics. Cancer Drug Discovery and Development. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9135-4_14

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