Abstract
Background: DNA topoisomerase II-α (Top2-α), an essential enzyme for the management of DNA during replication, transcription, recombination, and chromatin remodeling, is one of the most important anticancer targets. Numerous molecules have been designed as Top2-α inhibitors. However, several studies have shown that polymorphisms and mutations in Top2 have conferred resistance to most of these anticancer drugs. The aim of this study was to computationally examine the mechanisms by which genomic variations in Top2-α could affect its resistance to Amsacrine and Mitoxantrone as important inhibitors of the enzyme.
Results: The results showed that variants K529E, R568H, R568G and T530M could affect Top2-α inhibition by Amsacrine causing possible drug-resistant. Moreover, R487K, and Y481C variants could change the response of the enzyme to Mitoxantrone. Conclusion: These results could facilitate the prediction and development of more effective drugs for Top2-α variants, making the cancer chemotherapy more effectivKeywords: Cancer therapy, drug-resistance, topoisomerase II, topoisomerase inhibitors, non-synonymous polymorphisms, docking.
Related Books
Frontiers in Clinical Drug Research - Anti-Cancer Agents
NEOPLASIA and FERTILITY
Breast Cancer: Current Trends in Molecular Research
The Evolution of Radionanotargeting towards Clinical Precision Oncology: A Festschrift in Honor of Kalevi Kairemo
Nanotherapeutics for the Treatment of Hepatocellular Carcinoma
Topics in Anti-Cancer Research
Frontiers in Clinical Drug Research - Anti-Cancer Agents
Modern Cancer Therapies and Traditional Medicine: An Integrative Approach to Combat Cancers
Herbal Medicine: Back to the Future
Thrombosis in Cancer: A Medical Professional's Guide to Cancer Associated Thrombosis
17
4