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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 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.
DOI: 10.1038/s41467-021-22582-6
ORCID: 0000-0003-2331-0434
PubMed URL: 33941784
Type: Journal Article
Appears in Collections:Journal articles

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