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Targeting DNA repair in cancer: current state and novel approaches

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Abstract

DNA damage response, DNA repair and genomic instability have been under study for their role in tumor initiation and progression for many years now. More recently, next-generation sequencing on cancer tissue from various patient cohorts have revealed mutations and epigenetic silencing of various genes encoding proteins with roles in these processes. These findings, together with the unequivocal role of DNA repair in therapeutic response, have fueled efforts toward the clinical exploitation of research findings. The successful example of PARP1/2 inhibitors has also supported these efforts and led to numerous preclinical and clinical trials with a large number of small molecules targeting various components involved in DNA repair singularly or in combination with other therapies. In this review, we focus on recent considerations related to DNA damage response and new DNA repair inhibition agents. We then discuss how immunotherapy can collaborate with these new drugs and how epigenetic drugs can rewire the activity of repair pathways and sensitize cancer cells to DNA repair inhibition therapies.

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Acknowledgements

This work was supported by a Worldwide Cancer Research Grant (16/1217) and Horizon 2020 Grants (732309 and 801347) to AK, and a Greek General Secretariat for Research and Technology and the Hellenic Foundation for Research and Innovation (HFRI) Grant (472-EpiNotch) to TR.

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Authors and Affiliations

  1. Biomedical Research Foundation of the Academy of Athens, 11527, Athens, Greece

    Apostolos Klinakis & Theodoros Rampias

  2. Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA

    Dimitris Karagiannis

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  1. Apostolos Klinakis
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  2. Dimitris Karagiannis
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  3. Theodoros Rampias
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Correspondence to Apostolos Klinakis or Theodoros Rampias.

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Klinakis, A., Karagiannis, D. & Rampias, T. Targeting DNA repair in cancer: current state and novel approaches. Cell. Mol. Life Sci. 77, 677–703 (2020). https://doi.org/10.1007/s00018-019-03299-8

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  • DOI: https://doi.org/10.1007/s00018-019-03299-8

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