DNA repair inhibitors to enhance radiotherapy: Progresses and limitations

Radiotherapy is one of the most common form of treatment in oncology care. Indeed, radiotherapy proved to be very effective in treating a wide range of malignancies. Nevertheless, certain tumours are intrinsically radioresistant or may evolve to become radioresistant. Resistance to radiotherapy is often associated with dysregulated DNA damage response and repair. Recently, a number of strategies have been developed to improve radiotherapy efficacy by targeting the DNA damage response and repair pathways. Ongoing clinical trials showed the potential of some of these approaches in enhancing radiotherapy, but also highlighted the possible limitations. Here, we will describe (i) the main mechanisms involved in double-strand break repair; (ii) available strategies that target these DNA repair processes to improve radiotherapy and (iii) the clinical outcomes and challenges that have emerged so far.