Turning on the radio: Epigenetic inhibitors as potential radiopriming agents

Bryan Oronsky, Jan Scicinski, Michelle M. Kim, Pedro Cabrales, Michael E. Salacz, Corey A. Carter, Neil Oronsky, Harry Lybeck, Michelle Lybeck, Christopher Larson, Tony R. Reid, Arnold Oronsky

Research output: Contribution to journalReview articlepeer-review


First introduced during the late 1800s, radiation therapy is fundamental to the treatment of cancer. In developed countries, approximately 60% of all patients receive radiation therapy (also known as the sixty percenters), which makes radioresistance in cancer an important and, to date, unsolved, clinical problem. Unfortunately, the therapeutic refractoriness of solid tumors is the rule not the exception, and the ubiquity of resistance also extends to standard chemotherapy, molecularly targeted therapy and immunotherapy. Based on extrapolation from recent clinical inroads with epigenetic agents to prime refractory tumors for maximum sensitivity to concurrent or subsequent therapies, the radioresistant phenotype is potentially reversible, since aberrant epigenetic mechanisms are critical contributors to the evolution of resistant subpopulations of malignant cells. Within the framework of a syllogism, this review explores the emerging link between epigenetics and the development of radioresistance and makes the case that a strategy of pre- or co-treatment with epigenetic agents has the potential to, not only derepress inappropriately silenced genes, but also increase reactive oxygen species production, resulting in the restoration of radiosensitivity.

Original languageEnglish (US)
Article number32
Issue number3
StatePublished - Sep 2016


  • DNA methyltransferase inhibition
  • Epigenetic priming
  • Epigenetics
  • Histone deacetylase inhibition
  • Radiosensitization
  • Radiotherapy
  • Reactive oxygen species (ROS)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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