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.
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2020-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-16393-4 |
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doaj-e147f3013f3440d1be5ac0b31368773d |
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doaj-e147f3013f3440d1be5ac0b31368773d2021-05-30T11:16:09ZengNature Publishing GroupNature Communications2041-17232020-05-0111111810.1038/s41467-020-16393-4CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancerElaine Sanij0Katherine M. Hannan1Jiachen Xuan2Shunfei Yan3Jessica E. Ahern4Anna S. Trigos5Natalie Brajanovski6Jinbae Son7Keefe T. Chan8Olga Kondrashova9Elizabeth Lieschke10Matthew J. Wakefield11Daniel Frank12Sarah Ellis13Carleen Cullinane14Jian Kang15Gretchen Poortinga16Purba Nag17Andrew J. Deans18Kum Kum Khanna19Linda Mileshkin20Grant A. McArthur21John Soong22Els M. J. J. Berns23Ross D. Hannan24Clare L. Scott25Karen E. Sheppard26Richard B. Pearson27Peter MacCallum Cancer CentreACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National UniversityPeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchThe Walter and Eliza Hall Institute of Medical ResearchPeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreQIMR Berghofer Medical Research InstituteDepartment of Medicine, St. Vincent’s Hospital, University of MelbourneQIMR Berghofer Medical Research InstitutePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreSenhwa Biosciences, Virginia Commonwealth University School of MedicineDepartment of Medical Oncology, Erasmus MC Cancer InstitutePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentrePeter MacCallum Cancer CentreAcquired 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.https://doi.org/10.1038/s41467-020-16393-4 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
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 |
| spellingShingle |
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 CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer Nature Communications |
| author_facet |
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 |
| author_sort |
Elaine Sanij |
| title |
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| title_short |
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| title_full |
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| title_fullStr |
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| title_full_unstemmed |
CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| title_sort |
cx-5461 activates the dna damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer |
| publisher |
Nature Publishing Group |
| series |
Nature Communications |
| issn |
2041-1723 |
| publishDate |
2020-05-01 |
| description |
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. |
| url |
https://doi.org/10.1038/s41467-020-16393-4 |
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