Selective inhibitors of DNA-PK have demonstrated radio sensitization in preclinical investigations (Shinohara et al., 2005; Davidson et al., 2013; Ismail et al., 2004) Currently, three phase 1 clinical-trial are underway to evaluate the safety and tolerability of a DNA-PK inhibitor (M3814) in combination with palliative RT with or without IT for advanced solid tumors (NCT02516813 and NCT03724890), as well as in combination with curative-intent RT for locally advanced rectal cancer (NCT03770689). Here, PRKDC is linked to rectal cancer.