CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer
Acquired resistance limits the efficacy of PARP inhibitors (PARPi) in high grade serous ovarian cancer (HGSOC). Here, the authors show that inhibition of RNA polymerase I transcription using CX-5461 increases the therapeutic efficacy of PARPi and overcomes PARPi resistance in PDX models of HGSOC.
Main Authors: | Elaine Sanij, Katherine M. Hannan, Jiachen Xuan, Shunfei Yan, Jessica E. Ahern, Anna S. Trigos, Natalie Brajanovski, Jinbae Son, Keefe T. Chan, Olga Kondrashova, Elizabeth Lieschke, Matthew J. Wakefield, Daniel Frank, Sarah Ellis, Carleen Cullinane, Jian Kang, Gretchen Poortinga, Purba Nag, Andrew J. Deans, Kum Kum Khanna, Linda Mileshkin, Grant A. McArthur, John Soong, Els M. J. J. Berns, Ross D. Hannan, Clare L. Scott, Karen E. Sheppard, Richard B. Pearson |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2020-05-01
|
Series: | Nature Communications |
Online Access: | https://doi.org/10.1038/s41467-020-16393-4 |
Similar Items
-
rDNA Chromatin Activity Status as a Biomarker of Sensitivity to the RNA Polymerase I Transcription Inhibitor CX-5461
by: Jinbae Son, et al.
Published: (2020-07-01) -
CX-5461 can destabilize replication forks in PARP inhibitor-resistant models of ovarian cancer
by: Jiachen Xuan, et al.
Published: (2020-11-01) -
CX-5461 Enhances the Efficacy of APR-246 via Induction of DNA Damage and Replication Stress in Triple-Negative Breast Cancer
by: Ashwini Makhale, et al.
Published: (2021-05-01) -
The primary mechanism of cytotoxicity of the chemotherapeutic agent CX-5461 is topoisomerase II poisoning
by: Bruno, Peter M, et al.
Published: (2021) -
Ubiquitin-mediated DNA damage response is synthetic lethal with G-quadruplex stabilizer CX-5461
by: Tehmina Masud, et al.
Published: (2021-05-01)