A RAD51 assay feasible in routine tumor samples calls inhibitor response beyond BRCA mutation

Poly(-ribose) polymerase () inhibitors (i) are effective in cancers with defective homologous recombination repair (), including 1/2-related cancers. A test to identify additional -deficient tumors will help to extend their use in new indications. We evaluated the activity of the i olaparib in patie...

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Autores: Castroviejo-Bermejo, Marta|||0000-0002-8540-5837, Cruz Zambrano, Cristina|||0000-0002-6474-7504, Llop Guevara, Alba|||0000-0002-7913-9472, Gutiérrez-Enríquez, Sara|||0000-0002-1711-6101, Ducy, Mandy, Ibrahim, Yasir Hussein, Gris-Oliver, Albert|||0000-0003-1802-9541, Pellegrino, Benedetta, Bruna, Alejandra|||0000-0003-1214-9665, Guzmán, Marta|||0000-0002-0924-9887, Rodríguez, Olga|||0000-0002-0123-9975, Grueso, Judit|||0000-0003-1093-7940, Bonache, Sandra|||0000-0002-7395-8143, Moles-Fernández, Alejandro|||0000-0003-0252-6084, Villacampa Javierre, Guillermo|||0000-0003-4868-6585, Viaplana, Cristina|||0000-0001-8904-4330, Gómez Pardo, Patricia, Vidal, Marc, Peg, Vicente|||0000-0002-5203-6166, Serres Creixams, Xavier|||0000-0001-8642-467X, Dellaire, Graham, Simard, Jacques|||0000-0001-6906-3390, Nuciforo, Paolo|||0000-0003-1380-0990, Rubio, Isabel T.|||0000-0003-0035-0679, Dientsmann, Rodrigo, Barrett, J. Carl|||0000-0003-4042-9859, Caldas, Carlos|||0000-0003-3547-1489, Baselga Torres, Josep, Saura Manich, Cristina|||0000-0001-8296-5065, Cortés Castán, Javier|||0000-0001-7623-1583, Déas, Olivier, Jonkers, Jos|||0000-0002-9264-9792, Masson, Jean-Yves, Cairo, Stefano, Judde, Jean-Gabriel, O'Connor, Mark J.|||0000-0003-1823-625X, Diez, Orland|||0000-0001-7339-0570, Balmaña Gelpí, Judith|||0000-0002-0762-6415, Serra, Violeta|||0000-0001-6620-1065
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:253701
Acceso en línea:https://ddd.uab.cat/record/253701
https://dx.doi.org/urn:doi:10.15252/emmm.201809172
Access Level:acceso abierto
Palabra clave:1
Homologous recombination
2
Inhibitors
51
Biomarkers & Diagnostic Imaging
Cancer
Pharmacology & Drug Discovery
Descripción
Sumario:Poly(-ribose) polymerase () inhibitors (i) are effective in cancers with defective homologous recombination repair (), including 1/2-related cancers. A test to identify additional -deficient tumors will help to extend their use in new indications. We evaluated the activity of the i olaparib in patient-derived tumor xenografts (s) from breast cancer () patients and investigated mechanisms of sensitivity through exome sequencing, 1 promoter methylation analysis, and immunostaining of proteins, including 51 nuclear foci. In an independent panel, the predictive capacity of the 51 score and the homologous recombination deficiency () score were compared. To examine the clinical feasibility of the 51 assay, we scored archival breast tumor samples, including 2-related hereditary cancers. The 51 score was highly discriminative of i sensitivity versus PARPi resistance in s and outperformed the genomic test. In clinical samples, all 2-related tumors were classified as -deficient by the 51 score. The functional biomarker 51 enables the identification of i-sensitive and broadens the population who may benefit from this therapy beyond 1/2-related cancers.

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