ABSTRACT
The therapeutic efficacy of TMZ, a common used drug for chemotherapy, is limited by the resistance from colorectal cancer cells. Base excision repair (BER) pathway has been identified as one of the reasons for drug resistance. By blocking Polß-dependent BER (Base Excision Repair) pathway, the efficacy of TMZ treatment can be improved greatly. Several Polß inhibitors that have been identified could not become approved drugs due to lack of potency or specificity. To find therapeutic candidates with exquisite specificity and high affinity to Polß, phage display technology was used in the current research. We screened out a candidate Polß inhibitor, 10 D, that can inhibit the activity of Polßand SP-BER (Short-Patch Base excision Repair) pathway. Co-treatment with 10 D enhanced the sensitivity of colorectal cancer (CRC) cells to TMZ both in vitro and in vivo. Our data suggested that the novel Polß inhibitor we identified can improve TMZ efficacy and optimize CRC chemotherapy.
