Base Excision Repair Capacity in Non-Muscle-Invasive Bladder Cancer

Bladder cancer (BC) is the ninth most frequently diagnosed cancer and non-muscle-invasive BC (NMIBC) occupies the majority of BCs at diagnosis. In the treatment of the disease, bladder tumors are surgically removed and adjuvant therapy subsequently continues with chemotherapeutic drugs. These chemotherapeutic drugs show their cytotoxic effects by generating several types of damages on DNA, including oxidative DNA damage. Base excision repair (BER) mechanism is the main mechanisms that plays role in repairing the damage of these drugs. Balance of BER capacity is crucial for ensuring genomic stability and preventing drug resistance. How the patients’ BER capacity affects NMIBC is not known yet. Therefore, in this study, it was aimed to investigate key BER enzymes activities and overall BER capacity in patients diagnosed with NMIBC. In this study, the enzyme activities were measured dependent on radioactivity in patients’ NMIBC and corresponding normal tissues by using substrates that are peculiar to each enzyme. As a consequence, high-grade NMIBC tissues have been shown to have enhanced overall BER capacity due to increased UDG, APE1 and Pol β activities. Furthermore, inter-individual variations in the BER capacity have been demonstrated. Thus, these findings suggest that the increased in BER capacity of NMIBC due to increased UDG, APE1 and/or Pol β activities can enhance the chemotherapeutic resistance to NMIBC and contribute to progression of NMIBC. Moreover, UDG, APE1 and/or Pol β can be used as a predictive, prognostic and therapeutic target for NMIBC. Furthermore, inter-individual variations in BER capacity may contribute to the development of personalized therapy approaches for NMIBC cases