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

  • Pratik Nagaria
  • Feyruz V. RassoolEmail author
Part of the Cancer Drug Discovery and Development book series (CDD&D)


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.


Alternative non-homologous end-joining Microhomology-mediated end joining PARP1 Double-strand break repair Cancer therapeutics Genomic instability 


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Radiation Oncology and Marlene and Stewart Greenebaum Comprehensive Cancer CenterUniversity of Maryland School of MedicineBaltimoreUSA
  2. 2.BioReliance Corporation, A MilliporeSigma CompanyRockvilleUSA

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