A novel polymerase β inhibitor from phage displayed peptide library augments the anti-tumour effects of temozolomide on colorectal cancer.

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 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 in vitro and in vivo. Our data suggested that the novel Polβ inhibitor we identified can improve TMZ efficacy and optimize CRC chemotherapy.

• Authors: Lihong Qin, Mao Huiwen, Jianguo Wang, Yuanyaun Wang, Salman A Khan, Ying Zhang, Hong Qiu, Longwei Jiang, Lingfeng He, Yan Zhang, Shaochang Jia
• Journal: Journal of chemotherapy (Florence, Italy) (J Chemother) Vol. 34 Issue 6 Pg. 391-400 (Oct 2022) ISSN: 1973-9478 [Electronic] England
• PMID: 34870566 (Publication Type: Journal Article)

Chemical References

• Peptide Library
• DNA Polymerase beta
• Temozolomide

Topics

• Bacteriophages (metabolism)
• Colorectal Neoplasms (drug therapy, pathology)
• DNA Polymerase beta (genetics, metabolism)
• DNA Repair
• Humans
• Peptide Library
• Temozolomide (pharmacology, therapeutic use)