In this study, we aimed to (1) validate the radio-sensitizing effects of the ATRi Ceralasertib from our previous study by using patient-derived SCC (p-SCC) and UC (p-UC) ex vivo cultures, (2) characterize compensatory DNA repair mechanisms arising from resistant ATRi-adaptation, and (3) evaluate the efficacy of targeted compensatory pathways by inhibition of HR repair pathway to overcome ATRi induced resistance and to bypass mechanisms of ATR mutated BLCA. This evidence concerns the gene ATR and bladder transitional cell carcinoma.