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https://ahro.austin.org.au/austinjspui/handle/1/26424| Title: | Molecular and clinical determinants of response and resistance to rucaparib for recurrent ovarian cancer treatment in ARIEL2 (Parts 1 and 2). | Austin Authors: | 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 | Affiliation: | Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain University of California Los Angeles, Los Angeles, CA, USA Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada BC Cancer-Vancouver, Vancouver, BC, Canada l'Université de Montréal (CHUM), Montréal, QC, Canada Lawson Health Research Institute, London, ON, Canada Tom Baker Cancer Center, Calgary, AB, Canada GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France Gustave Roussy Cancer Center and INSERM U981, Villejuif, France Guy's and St. Thomas NHS Foundation Trust, London, UK University of Washington, Seattle, WA, USA The University of Texas, MD Anderson Cancer Center, Houston, TX, USA Memorial Sloan Kettering Cancer Center, New York, NY, USA Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia Surgery (University of Melbourne) Stanford University Cancer Center and Stanford Cancer Institute, Palo Alto, CA, USA Clovis Oncology, Inc., Boulder, CO, USA University of Arizona Cancer Center, Tucson, AZ, USA Foundation Medicine, Inc., Cambridge, MA, USA Mayo Clinic, Rochester, MN, USA Imperial College London, London, UK Rocky Mountain Cancer Centers, Lakewood, CO, USA University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA The Ohio State University, James Cancer Center, Columbus, OH, USA |
Issue Date: | 3-May-2021 | Date: | 2021-05-03 | Publication information: | Nature Communications 2021; 12(1): 2487 | Abstract: | 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. | URI: | https://ahro.austin.org.au/austinjspui/handle/1/26424 | DOI: | 10.1038/s41467-021-22582-6 | ORCID: | 0000-0003-2331-0434 0000-0002-8109-4023 0000-0003-2472-8306 0000-0003-1902-3256 0000-0002-2371-0844 0000-0003-3825-1326 0000-0002-1976-5201 0000-0002-4900-7145 0000-0003-0105-9760 0000-0002-3689-5956 0000-0002-9387-7586 |
Journal: | Nature Communications | PubMed URL: | 33941784 | Type: | Journal Article |
| Appears in Collections: | Journal articles |
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