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dc.contributor.authorGirotti, Maria Romina
dc.contributor.authorGremel, Gabriela
dc.contributor.authorLee, Rebecca J
dc.contributor.authorGalvani, Elena
dc.contributor.authorRothwell, Dominic G
dc.contributor.authorViros, Amaya
dc.contributor.authorMandal, Amit Kumar
dc.contributor.authorLim, Kok Haw Jonathan
dc.contributor.authorSaturno, Grazia
dc.contributor.authorFurney, Simon J
dc.contributor.authorBaenke, Franziska
dc.contributor.authorPedersen, M
dc.contributor.authorRogan, Jane
dc.contributor.authorSwan, Jacqueline
dc.contributor.authorSmith, Matthew
dc.contributor.authorFusi, Alberto
dc.contributor.authorOudit, Deemesh
dc.contributor.authorDhomen, Nathalie
dc.contributor.authorBrady, Ged
dc.contributor.authorLorigan, Paul C
dc.contributor.authorDive, Caroline
dc.contributor.authorMarais, Richard
dc.date.accessioned2016-01-22T13:54:22Zen
dc.date.available2016-01-22T13:54:22Zen
dc.date.issued2015-12-29en
dc.identifier.citationApplication of sequencing, liquid biopsies and patient-derived xenografts for personalized medicine in melanoma. 2015: Cancer Discoven
dc.identifier.issn2159-8290en
dc.identifier.pmid26715644en
dc.identifier.doi10.1158/2159-8290.CD-15-1336en
dc.identifier.urihttp://hdl.handle.net/10541/594593en
dc.description.abstractTargeted and immunotherapies have transformed melanoma care, extending median survival from ~9 to over 25 months but nevertheless, most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end we developed protocols to facilitate individualized treatment decisions for advanced melanoma patients, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF mutant tumors, which were then validated in patient-derived xenografts (PDXs). We also developed circulating tumor cell-derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine of melanoma patients.
dc.languageENGen
dc.language.isoenen
dc.rightsArchived with thanks to Cancer discoveryen
dc.titleApplication of sequencing, liquid biopsies and patient-derived xenografts for personalized medicine in melanoma.en
dc.typeArticleen
dc.contributor.departmentMolecular Oncology Group, Cancer Research UK Manchester Instituteen
dc.identifier.journalCancer Discoveryen
html.description.abstractTargeted and immunotherapies have transformed melanoma care, extending median survival from ~9 to over 25 months but nevertheless, most patients still die of their disease. The aim of precision medicine is to tailor care for individual patients and improve outcomes. To this end we developed protocols to facilitate individualized treatment decisions for advanced melanoma patients, analyzing 364 samples from 214 patients. Whole exome sequencing (WES) and targeted sequencing of circulating tumor DNA (ctDNA) allowed us to monitor responses to therapy and to identify and then follow mechanisms of resistance. WES of tumors revealed potential hypothesis-driven therapeutic strategies for BRAF wild-type and inhibitor-resistant BRAF mutant tumors, which were then validated in patient-derived xenografts (PDXs). We also developed circulating tumor cell-derived xenografts (CDX) as an alternative to PDXs when tumors were inaccessible or difficult to biopsy. Thus, we describe a powerful technology platform for precision medicine of melanoma patients.


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