Journal article
Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs
E Leung, J Patel, JA Hollywood, A Zafar, P Tomek, D Barker, LI Pilkington, M van Rensburg, RJ Langley, NA Helsby, CJ Squire, BC Baguley, WA Denny, J Reynisson, IKH Leung
Oncology and Therapy | SPRINGER | Published : 2021
Abstract
Cancer chemotherapy sensitizers hold the key to maximizing the potential of standard anticancer treatments. We have a long-standing interest in developing and validating inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) as chemosensitizers for topoisomerase I poisons such as topotecan. Herein, by using thieno[2,3-b]pyridines, a class of TDP1 inhibitors, we showed that the inhibition of TDP1 can restore sensitivity to topotecan, results that are supported by TDP1 knockout cell experiments using CRISPR/Cas9. However, we also found that the restored sensitivity towards topoisomerase I inhibitors is likely regulated by multiple complementary DNA repair pathways. Our resu..
View full abstractGrants
Awarded by New Zealand Government
Funding Acknowledgements
We thank the financial support of the University of Auckland and the Auckland Cancer Society Research Centre. E.L. acknowledges the support of a Belinda Scott Science Fellowship from the New Zealand Breast Cancer Foundation, a Lottery Health Research Grant from the New Zealand Government, and a research project grant from the Cancer Research Trust New Zealand. D.B. acknowledges the support of a research grant from the Cancer Society of New Zealand (20.23). P.T. acknowledges the support from a John Gavin Post-doctoral Fellowship (GOT 1717 JGPDF) awarded to P.T. by Cancer Research Trust New Zealand. Sponsorship for the Rapid Service Fee was funded by the Cancer Research Trust New Zealand.