Clinical Research Papers:
Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions
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Berglind O. Einarsdottir1,4, Roger Olofsson Bagge1,4, Joydeep Bhadury1,4, Henrik Jespersen2,4, Jan Mattsson1,4, Lisa M. Nilsson1,4, Katarina Truvé5, Marcela Dávila López4,5, Peter Naredi1,4, Ola Nilsson3,4, Ulrika Stierner2,4, Lars Ny2,4 and Jonas A. Nilsson1,4
1 Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
2 Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
3 Department of Biomedicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden
4 Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden
5 The Bioinformatics Core Facility at the University of Gothenburg, Gothenburg, Sweden
Jonas Nilsson, email:
Keywords: melanoma, mouse models, patient-derived xenografts
Received: August 18, 2014 Accepted: September 07, 2014 Published: September 08, 2014
The development of novel therapies against melanoma would benefit from individualized tumor models to ensure the rapid and accurate identification of biomarkers of therapy response. Previous studies have suggested that patient-derived xenografts (PDXes) could be useful. However, the utility of PDXes in guiding real-time treatment decisions has only been reported in anecdotal forms. Here tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice to generate PDXes. 23/26 melanoma biopsies generated serially transplantable PDX models, and their histology, mutation status and expression profile resembled their corresponding patient biopsy. The potential treatment for one patient was revealed by an in vitro drug screen and treating PDXes with the MEK inhibitor trametinib. In another patient, the BRAF mutation predicted the response of both the patient and its corresponding PDXes to MAPK-targeted therapy. Importantly, in this unselected group of patients, the time from biopsy for generation of PDXes until death was significantly longer than the time required to reach the treatment phase of the PDXes. Thus, it could be clinically meaningful to use this type of platform for melanoma patients as a pre-selection tool in clinical trials.
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