Changzhou No. 7 People's Hospital, Changzhou, China.
Shuyang Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Shuyang, China.
J Chemother. 2022 Oct;34(6):391-400. doi: 10.1080/1120009X.2021.2009987. Epub 2021 Dec 6.
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 Polβ-dependent BER (Base Excision Repair) pathway, the efficacy of TMZ treatment can be improved greatly. Several Polβ 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 Polβ, phage display technology was used in the current research. We screened out a candidate Polβ inhibitor, 10 D, that can inhibit the activity of Polβand SP-BER (Short-Patch Base excision Repair) pathway. Co-treatment with 10 D enhanced the sensitivity of colorectal cancer (CRC) cells to TMZ both and . Our data suggested that the novel Polβ inhibitor we identified can improve TMZ efficacy and optimize CRC chemotherapy.
替莫唑胺（TMZ）是一种常用的化疗药物，但疗效有限，其耐药性与结直肠癌细胞有关。碱基切除修复（BER）途径已被确定为耐药的原因之一。通过阻断 Polβ依赖性 BER（碱基切除修复）途径，可以显著提高 TMZ 的治疗效果。已鉴定出的几种 Polβ抑制剂由于效力或特异性不足而未能成为批准药物。为了寻找具有高特异性和高亲和力的治疗候选物，本研究采用噬菌体展示技术。我们筛选出一种候选 Polβ抑制剂 10D，它可以抑制 Polβ的活性和 SP-BER（短补丁碱基切除修复）途径。10D 与 TMZ 联合治疗可增强 CRC 细胞对 TMZ 的敏感性。我们的数据表明，我们鉴定的新型 Polβ抑制剂可以提高 TMZ 的疗效并优化 CRC 化疗。
