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DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance

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Handbook of Anticancer Pharmacokinetics and Pharmacodynamics

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

Abstract

DNA excision repair plays a significant part in platinum-based chemotherapy by removing DNA lesions caused by platinum-containing drugs. The nucleotide excision repair (NER) pathway is the mammalian DNA repair mechanism that removes bulky DNA adducts induced by DNA damaging chemotherapeutic agents. Platinum compounds induce their cytotoxic effect by binding to a DNA molecule in the form of a platinum-DNA-adduct. The NER pathway is the main mechanism responsible for platinum resistance by increased platinum-DNA-adduct removal and the excision repair cross complementing-group 1 (ERCC1) gene plays a major role in the NER-pathway because of its damage recognition and excision ability. This chapter will review mechanisms of DNA repair and platinum resistance as it relates to the NER pathway and regulation of ERCC1. A brief discussion on the role of cancer stem cells in platinum resistance is also presented.

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Authors and Affiliations

  1. National Institute on Minority Health and Health Disparities, National Institutes of Health, 6707 Democracy Blvd., Bethesda, MD, 20892, USA

    Eddie Reed M.D.

  2. Mitchell Cancer Institute, University of South Alabama, 1660 Springhill Avenue, Mobile, AL, 36604-1405, USA

    Teri L. Larkins Ph.D.

  3. Center for Cancer Research, National Cancer Institute, 9000 Rockville Pike, Bldg 10/Rm 5A01, Bethesda, MD, 20892, USA

    Cindy H. Chau Ph.D. & William D. Figg

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  1. Eddie Reed M.D.
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Correspondence to Eddie Reed M.D. .

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Editors and Affiliations

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

    Michelle A. Rudek

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

    Cindy H. Chau

  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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Reed, E., Larkins, T.L., Chau, C.H., Figg, W.D. (2014). DNA Repair: ERCC1, Nucleotide Excision Repair, and Platinum Resistance. 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_18

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