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, 6 (Suppl 5), S822-S839

Repurposing DNA Repair Factors to Eradicate Tumor Cells Upon Radiotherapy

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Repurposing DNA Repair Factors to Eradicate Tumor Cells Upon Radiotherapy

Souparno Bhattacharya et al. Transl Cancer Res.

Abstract

Cancer is the leading cause of death worldwide. Almost 50% of all cancer patients undergo radiation therapy (RT) during treatment, with varying success. The main goal of RT is to kill tumor cells by damaging their DNA irreversibly while sparing the surrounding normal tissue. The outcome of RT is often determined by how tumors recognize and repair their damaged DNA. A growing body of evidence suggests that tumors often show abnormal expression of DNA double-strand break (DSB) repair genes that are absent from normal cells. Defects in a specific DNA repair pathway make tumor cells overly dependent on alternative or backup pathways to repair their damaged DNA. These tumor cell-specific abnormalities in the DNA damage response (DDR) machinery can potentially be used as biomarkers for treatment outcomes or as targets for sensitization to ionizing radiation (IR). An improved understanding of genetic or epigenetic alterations in the DNA repair pathways specific to cancer cells has paved the way for new treatments that combine pharmacological exploitation of tumor-specific molecular vulnerabilities with IR. Inhibiting DNA repair pathways has the potential to greatly enhance the therapeutic ratio of RT. In this review, we will discuss DNA repair pathways in active cells and how these pathways are deregulated in tumors. We will also describe the impact of targeting cancer-specific aberrations in the DDR as a treatment strategy to improve the efficacy of RT. Finally, we will address the current roadblocks and future prospects of these approaches.

Keywords: DNA damage; DNA repair; Ionizing radiation (IR); cancer; charged particle therapy (CPT); radiotherapy; synthetic lethality.

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematics of direct and indirect effects of ionizing radiation and strategies for the therapeutic intervention. ROS, reactive oxygen species; PARP, poly (ADP-ribose) polymerase; IR, ionizing radiation; ATM, ataxia telangiectasia mutated.

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