Repurposing DNA repair factors to eradicate tumor cells upon radiotherapy

Souparno Bhattacharya, Aroumougame Asaithamby

Research output: Contribution to journalReview article

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)S822-S839
JournalTranslational Cancer Research
Volume6
DOIs
StatePublished - Jul 1 2017

Fingerprint

DNA Repair
Radiotherapy
Neoplasms
Ionizing Radiation
DNA Damage
DNA
Double-Stranded DNA Breaks
Therapeutics
Epigenomics
Cause of Death
Biomarkers
Pharmacology

Keywords

  • Cancer
  • Charged particle therapy (CPT)
  • DNA damage
  • DNA repair
  • Ionizing radiation (IR)
  • Radiotherapy
  • Synthetic lethality

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Repurposing DNA repair factors to eradicate tumor cells upon radiotherapy. / Bhattacharya, Souparno; Asaithamby, Aroumougame.

In: Translational Cancer Research, Vol. 6, 01.07.2017, p. S822-S839.

Research output: Contribution to journalReview article

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