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| Home > Articles > Published articles > Personalized cancer therapy prioritization based on driver alteration co-occurrence patterns |
(Vall d'Hebron Institut d'Oncologia) (Memorial Sloan Kettering Cancer Center) (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular) (Vall d'Hebron Institut d'Oncologia) (Vall d'Hebron Institut d'Oncologia) (Institució Catalana de Recerca i Estudis Avançats)
| Date: | 2020 |
| Abstract: | Identification of actionable genomic vulnerabilities is key to precision oncology. Utilizing a large-scale drug screening in patient-derived xenografts, we uncover driver gene alteration connections, derive driver co-occurrence (DCO) networks, and relate these to drug sensitivity. Our collection of 53 drug-response predictors attains an average balanced accuracy of 58% in a cross-validation setting, rising to 66% for a subset of high-confidence predictions. We experimentally validated 12 out of 14 predictions in mice and adapted our strategy to obtain drug-response models from patients' progression-free survival data. Our strategy reveals links between oncogenic alterations, increasing the clinical impact of genomic profiling. |
| Grants: | Ministerio de Economía y Competitividad BIO2016-77038-R Agència de Gestió d'Ajuts Universitaris i de Recerca VEIS001-P-001 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-540 Instituto de Salud Carlos III CPII19-00033 |
| Note: | Altres ajuts: L.M. is a recipient of an FPI fellowship. P.A. acknowledges the support of the Spanish Ministerio de Economía y Competitividad, the European Research Council (SysPharmAD: 614944), and the Generalitat de Catalunya. V.S. is a recipient of a Miguel Servet grant from ISCIII and receives funds from AGAUR (). The PDX program is supported by a GHD-Pink (FERO foundation) grant to V.S., A.G.-O. and M.P. received a FI-AGAUR and a Juan de la Cierva (MJCI-2015-25412) fellowship, respectively. M.S., P.R., and S.C. acknowledge the support of the NIH grants P30 CA008748, RO1CA190642, and the Breast Cancer Research Foundation. Additionally, P.R. receives funds from the Breast Cancer Alliance. |
| 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: | Drug-response biomarkers ; Driver co-occurrence networks ; Precision oncology |
| Published in: | Genome Medicine, Vol. 12 (september 2020) , ISSN 1756-994X |
