title: Melanoma patient-derived xenografts accurately model the disease and develop fast enough to guide treatment decisions.
abstract: 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.
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Berglind O
authors.initials: BO
authors.lastname: Einarsdottir
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Roger Olofsson
authors.initials: RO
authors.lastname: Bagge
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Joydeep
authors.initials: J
authors.lastname: Bhadury
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Henrik
authors.initials: H
authors.lastname: Jespersen
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Mattsson
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Nilsson
authors.affiliation: The Bioinformatics Core Facility at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Katarina
authors.initials: K
authors.lastname: Truvé
authors.affiliation: Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden. The Bioinformatics Core Facility at the University of Gothenburg, Gothenburg, Sweden.
authors.forename: Marcela Dávila
authors.initials: MD
authors.lastname: López
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Naredi
authors.affiliation: Department of Biomedicine, Institute of Biomedicine, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Nilsson
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Ulrika
authors.initials: U
authors.lastname: Stierner
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Ny
authors.affiliation: Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. Sahlgrenska Translational Melanoma Group at the Sahlgrenska Cancer Center, Gothenburg, Sweden.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D008875:Middle Aged; D057285:Precision Medicine; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays / Q000379:methods*