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Cell Death Signaling in Cancer Biology and Treatment pp 137–180Cite as

Targeting DNA Repair Pathways for Cancer Therapy

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Part of the book series: Cell Death in Biology and Diseases ((CELLDEATH))

Abstract

DNA repair pathways maintain the integrity of the genome, reducing the onset of cancer, disease, and aging. The majority of anticancer therapeutics (radiation and chemotherapy) function as genotoxins, eliciting genomic DNA damage in an attempt to induce cell death in the tumor. However, cellular DNA repair proteins counteract the effectiveness of these therapeutic genotoxins by repairing and removing the cell death-inducing DNA lesions, implicating DNA repair proteins as prime targets for improving response to currently available anticancer regimens. To trigger a tumor-specific cell death response (with minimal normal cell toxicity), the level of genomic DNA damage must therefore surpass the DNA repair capacity of the tumor without overwhelming the DNA repair potential of normal tissue. Interestingly, cancer-specific DNA repair defects offer novel approaches for tumor-selective therapy. This has become highly relevant as it is suggested that most cancer cells are likely to be defective in some aspect of DNA repair. Herein, we describe the molecular pathways that participate in the repair of DNA damage induced by radiation- and chemotherapeutics and discuss strategies that are being developed to target DNA repair for cancer treatment and highlight key DNA repair inhibitors that can enhance response. Further, we present novel therapeutic strategies being considered to exploit inherent weaknesses in tumor cells such as defects in one or more DNA repair pathways or related processes that may provide the opportunity to selectively increase tumor-specific cell death.

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Authors and Affiliations

  1. Division of Biological Stress Response, The Netherlands Cancer Institute, NL, Amsterdam, The Netherlands

    Conchita Vens

  2. Department of Pharmacology and Chemical Biology, University of Pittsburgh Cancer Institute, Hillman Cancer Center; University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Robert W. Sobol

  3. Department of Human Genetics, University of Pittsburgh School of Public Health, Pittsburgh, PA, USA

    Robert W. Sobol

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  1. Conchita Vens
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Correspondence to Robert W. Sobol .

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  1. Department of Medicine, University of Pittsburgh Division of Hematology/Oncology, Pittsburgh, Pennsylvania, USA

    Daniel E. Johnson

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Vens, C., Sobol, R.W. (2013). Targeting DNA Repair Pathways for Cancer Therapy. In: Johnson, D. (eds) Cell Death Signaling in Cancer Biology and Treatment. Cell Death in Biology and Diseases. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-5847-0_6

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