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Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma

2015; American Association for Cancer Research; Volume: 6; Issue: 3 Linguagem: Inglês

10.1158/2159-8290.cd-15-1336

2159-8290

María Romina Girotti, Gabriela Gremel, Rebecca Lee, Elena Galvani, Dominic G. Rothwell, Amaya Virós, Amit Kumar Mandal, Kok Haw Jonathan Lim, Grazia Saturno, Simon J. Furney, Franziska Baenke, Malin Pedersen, Jane Rogan, Jacqueline Swan, Matthew Ryan Smith, Alberto Fusi, Deemesh Oudit, Nathalie Dhomen, Ged Brady, Paul Lorigan, Caroline Dive, Richard Marais,

CAR-T cell therapy research

Targeted therapies 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 patients with advanced melanoma, 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 (PDX). 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 in patients with melanoma.