Current trends and future perspectives in hadron therapy: radiobiology

Abstract

Abstract Purpose The purpose of this article was to highlight current and future trends in radiobiology in an effort to move hadron therapy forward through the application of new knowledge in DNA damage and subsequent response to heavy ion radiotherapy, immune oncology and the interconnection between. Methods The subject matter begins with a description of the role of radiation in eliciting either an immunogenic or tolerogenic response to radiation exposure. The role of fragmented DNA in an immunogenic response is described, followed by the definitive role that DNA damage and subsequent repair, or not, of complex DNA damage after hadron exposure plays in the survival response of hadron irradiated cells. Results The process by which ionizing radiation elicits an immunogenic rather than tolerogenic response is becoming clearer. The timing of fractionated radiotherapy when combined with an immune checkpoint inhibitor is not clear and may be tumor site specific. Furthermore, whether hadron therapy is more effective at generating a durable immunogenic response is unknown. Conclusions Cytosolic DNA plays a significant role in eliciting an innate immune response with the likelihood that hadron therapy would generate complex DNA damage that because it is less likely to be repaired, is more likely to become cytosolic DNA, and more likely to activate an immunogenic response. Lastly, DNA repair pathway choice appears to be a credible bio-indicator for hadron therapy selection as well identify druggable targets to enhance hadron therapy.