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Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2)
ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methyla...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
| Publicado: |
Nature Publishing Group UK
2021
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093258/ https://www.ncbi.nlm.nih.gov/pubmed/33941784 http://dx.doi.org/10.1038/s41467-021-22582-6 |
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| author | Swisher, Elizabeth M. Kwan, Tanya T. Oza, Amit M. Tinker, Anna V. Ray-Coquard, Isabelle Oaknin, Ana Coleman, Robert L. Aghajanian, Carol Konecny, Gottfried E. O’Malley, David M. Leary, Alexandra Provencher, Diane Welch, Stephen Chen, Lee-may Wahner Hendrickson, Andrea E. Ma, Ling Ghatage, Prafull Kristeleit, Rebecca S. Dorigo, Oliver Musafer, Ashan Kaufmann, Scott H. Elvin, Julia A. Lin, Douglas I. Chambers, Setsuko K. Dominy, Erin Vo, Lan-Thanh Goble, Sandra Maloney, Lara Giordano, Heidi Harding, Thomas Dobrovic, Alexander Scott, Clare L. Lin, Kevin K. McNeish, Iain A. |
| author_facet | Swisher, Elizabeth M. Kwan, Tanya T. Oza, Amit M. Tinker, Anna V. Ray-Coquard, Isabelle Oaknin, Ana Coleman, Robert L. Aghajanian, Carol Konecny, Gottfried E. O’Malley, David M. Leary, Alexandra Provencher, Diane Welch, Stephen Chen, Lee-may Wahner Hendrickson, Andrea E. Ma, Ling Ghatage, Prafull Kristeleit, Rebecca S. Dorigo, Oliver Musafer, Ashan Kaufmann, Scott H. Elvin, Julia A. Lin, Douglas I. Chambers, Setsuko K. Dominy, Erin Vo, Lan-Thanh Goble, Sandra Maloney, Lara Giordano, Heidi Harding, Thomas Dobrovic, Alexander Scott, Clare L. Lin, Kevin K. McNeish, Iain A. |
| author_sort | Swisher, Elizabeth M. |
| collection | PubMed |
| description | ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity. |
| format | Online Article Text |
| id | pubmed-8093258 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2021 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-80932582021-05-11 Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) Swisher, Elizabeth M. Kwan, Tanya T. Oza, Amit M. Tinker, Anna V. Ray-Coquard, Isabelle Oaknin, Ana Coleman, Robert L. Aghajanian, Carol Konecny, Gottfried E. O’Malley, David M. Leary, Alexandra Provencher, Diane Welch, Stephen Chen, Lee-may Wahner Hendrickson, Andrea E. Ma, Ling Ghatage, Prafull Kristeleit, Rebecca S. Dorigo, Oliver Musafer, Ashan Kaufmann, Scott H. Elvin, Julia A. Lin, Douglas I. Chambers, Setsuko K. Dominy, Erin Vo, Lan-Thanh Goble, Sandra Maloney, Lara Giordano, Heidi Harding, Thomas Dobrovic, Alexander Scott, Clare L. Lin, Kevin K. McNeish, Iain A. Nat Commun Article ARIEL2 (NCT01891344) is a single-arm, open-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinoma. In this post hoc exploratory biomarker analysis of pre- and post-platinum ARIEL2 samples, RAD51C and RAD51D mutations and high-level BRCA1 promoter methylation predict response to rucaparib, similar to BRCA1/BRCA2 mutations. BRCA1 methylation loss may be a major cross-resistance mechanism to platinum and PARPi. Genomic scars associated with homologous recombination deficiency are irreversible, persisting even as platinum resistance develops, and therefore are predictive of rucaparib response only in platinum-sensitive disease. The RAS, AKT, and cell cycle pathways may be additional modulators of PARPi sensitivity. Nature Publishing Group UK 2021-05-03 /pmc/articles/PMC8093258/ /pubmed/33941784 http://dx.doi.org/10.1038/s41467-021-22582-6 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Swisher, Elizabeth M. Kwan, Tanya T. Oza, Amit M. Tinker, Anna V. Ray-Coquard, Isabelle Oaknin, Ana Coleman, Robert L. Aghajanian, Carol Konecny, Gottfried E. O’Malley, David M. Leary, Alexandra Provencher, Diane Welch, Stephen Chen, Lee-may Wahner Hendrickson, Andrea E. Ma, Ling Ghatage, Prafull Kristeleit, Rebecca S. Dorigo, Oliver Musafer, Ashan Kaufmann, Scott H. Elvin, Julia A. Lin, Douglas I. Chambers, Setsuko K. Dominy, Erin Vo, Lan-Thanh Goble, Sandra Maloney, Lara Giordano, Heidi Harding, Thomas Dobrovic, Alexander Scott, Clare L. Lin, Kevin K. McNeish, Iain A. Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title_full | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title_fullStr | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title_full_unstemmed | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title_short | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2) |
| title_sort | molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ariel2 (parts 1 and 2) |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093258/ https://www.ncbi.nlm.nih.gov/pubmed/33941784 http://dx.doi.org/10.1038/s41467-021-22582-6 |
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