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Targeting the DNA Damage Response for Anti-Cancer Therapy pp 375–400Cite as

Alternative Non-homologous End-Joining: Mechanisms and Targeting Strategies in Cancer

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

Abstract

Repair of DNA double-strand breaks (DSB)s is essential to the growth and survival of normal as well as cancer cells. Alteration of DSB repair properties in cancer cells can not only drive genomic instability, but also confer increased sensitivity to DSB-inducing agents. Development of agents that selectively inhibit DSB repair pathways will facilitate the design of therapeutic strategies that exploit the differences in DSB repair properties between normal and cancer cells. While mechanisms for classic non-homologous end joining (C-NHEJ) and Homologous recombination (HR) DSB repair pathways have been well studied in cancer, less is known about the alternative and highly error-prone, ALT-NHEJ pathway. Here, we discuss the mechanisms for ALT-NHEJ, alterations in this repair pathway in cancer, inhibition of ALT-NHEJ and future directions for cancer therapies that target this pathway.

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Authors and Affiliations

  1. Department of Radiation Oncology and Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA

    Pratik Nagaria & Feyruz V. Rassool

  2. BioReliance Corporation, A MilliporeSigma Company, Rockville, MD, USA

    Pratik Nagaria

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  1. Pratik Nagaria
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  2. Feyruz V. Rassool
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Correspondence to Feyruz V. Rassool .

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  1. Vertex Pharmaceuticals (Europe) Ltd, Abingdon, Oxfordshire, United Kingdom

    John Pollard

  2. Northern Institute for Cancer Research, Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom

    Nicola Curtin

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Nagaria, P., Rassool, F.V. (2018). Alternative Non-homologous End-Joining: Mechanisms and Targeting Strategies in Cancer. In: Pollard, J., Curtin, N. (eds) Targeting the DNA Damage Response for Anti-Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Cham. https://doi.org/10.1007/978-3-319-75836-7_15

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