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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).
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.
Afiliación
  • Swisher EM; University of Washington, Seattle, WA, USA. swishere@uw.edu.
  • Kwan TT; Clovis Oncology, Inc., Boulder, CO, USA.
  • Oza AM; Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
  • Tinker AV; BC Cancer-Vancouver, Vancouver, BC, Canada.
  • Ray-Coquard I; GINECO, Centre Léon Bérard and University Claude Bernard, Lyon, France.
  • Oaknin A; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain.
  • Coleman RL; The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
  • Aghajanian C; Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Konecny GE; University of California Los Angeles, Los Angeles, CA, USA.
  • O'Malley DM; The Ohio State University, James Cancer Center, Columbus, OH, USA.
  • Leary A; Gustave Roussy Cancer Center and INSERM U981, Villejuif, France.
  • Provencher D; l'Université de Montréal (CHUM), Montréal, QC, Canada.
  • Welch S; Lawson Health Research Institute, London, ON, Canada.
  • Chen LM; University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
  • Wahner Hendrickson AE; Mayo Clinic, Rochester, MN, USA.
  • Ma L; Rocky Mountain Cancer Centers, Lakewood, CO, USA.
  • Ghatage P; Tom Baker Cancer Center, Calgary, AB, Canada.
  • Kristeleit RS; Guy's and St. Thomas NHS Foundation Trust, London, UK.
  • Dorigo O; Stanford University Cancer Center and Stanford Cancer Institute, Palo Alto, CA, USA.
  • Musafer A; University of Melbourne Department of Surgery, Austin Hospital, Heidelberg, VIC, Australia.
  • Kaufmann SH; Mayo Clinic, Rochester, MN, USA.
  • Elvin JA; Foundation Medicine, Inc., Cambridge, MA, USA.
  • Lin DI; Foundation Medicine, Inc., Cambridge, MA, USA.
  • Chambers SK; University of Arizona Cancer Center, Tucson, AZ, USA.
  • Dominy E; Clovis Oncology, Inc., Boulder, CO, USA.
  • Vo LT; Clovis Oncology, Inc., Boulder, CO, USA.
  • Goble S; Clovis Oncology, Inc., Boulder, CO, USA.
  • Maloney L; Clovis Oncology, Inc., Boulder, CO, USA.
  • Giordano H; Clovis Oncology, Inc., Boulder, CO, USA.
  • Harding T; Clovis Oncology, Inc., Boulder, CO, USA.
  • Dobrovic A; University of Melbourne Department of Surgery, Austin Hospital, Heidelberg, VIC, Australia.
  • Scott CL; Royal Melbourne Hospital and Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
  • Lin KK; Clovis Oncology, Inc., Boulder, CO, USA.
  • McNeish IA; Imperial College London, London, UK.
Nat Commun ; 12(1): 2487, 2021 05 03.
Article en En | MEDLINE | ID: mdl-33941784
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Carcinoma Epitelial de Ovario / Indoles / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Neoplasias Ováricas / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Carcinoma Epitelial de Ovario / Indoles / Antineoplásicos Tipo de estudio: Clinical_trials Límite: Adult / Aged / Aged80 / Female / Humans / Middle aged Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos