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| Home > Articles > Published articles > A RAD51 assay feasible in routine tumor samples calls inhibitor response beyond BRCA mutation |
| Home > Articles > Published articles > A RAD51 assay feasible in routine tumor samples calls inhibitor response beyond BRCA mutation |
(Vall d'Hebron Institut d'Oncologia) (Universitat Autònoma de Barcelona) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Instituto de Salud Carlos III) (Hospital Universitari Vall d'Hebron) (Vall d'Hebron Institut d'Oncologia) (Cancer Research UK (CRUK) Cambridge Cancer Centre) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (The Netherlands Cancer Institute (Amsterdam, Països Baixos)) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Instituto de Salud Carlos III)| Date: | 2018 |
| Abstract: | 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. |
| Grants: | Instituto de Salud Carlos III FIS PI17/01080 Ministerio de Economía y Competitividad CP14/00228 Ministerio de Economía y Competitividad CP16/00034 Ministerio de Economía y Competitividad PI12-02606 Ministerio de Economía y Competitividad PI12/02585 Ministerio de Economía y Competitividad PI15-00355 Ministerio de Economía y Competitividad PI13/01711 Ministerio de Economía y Competitividad PI16/01218 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017 SGR 540 |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | 1 ; Homologous recombination ; 2 ; Inhibitors ; 51 ; Biomarkers & Diagnostic Imaging ; Cancer ; Pharmacology & Drug Discovery |
| Published in: | EMBO Molecular Medicine, Vol. 10 (october 2018) , ISSN 1757-4684 |
