In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 14_Supplement ( 2015-07-15), p. B38-B38
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 used in biomarker of response discovery. However, the clinical utility of PDXes in guiding real-time treatment decisions have only been reported in anecdotal forms. In the present study we aimed to develop a platform of melanoma patient-derived xenografts (PDXes), to assess whether treatment responses in mice would be applicable as a pre-selection tool for clinical trials. To that end, tumor biopsies from patients with stage III and IV metastatic malignant melanoma were transplanted into immunocompromised mice. Most melanoma biopsies generated serially transplantable PDX models, and their histology, and mutation status resembled their corresponding patient biopsy. RNAseq demonstrated that the expression profiles of the tumors are maintained throughout several passages in mice. 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 MAP kinase pathway-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, we demonstrate that it would be clinically meaningful to use this type of platform for a large proportion of melanoma patients as a pre-selection tool in clinical trials. Citation Format: Berglind O. Einarsdottir, Roger Olofsson Bagge, Joydeep Bhadury, Henrik Jespersen, Lisa M. Nilsson, Jan Mattsson, Katarina Truvé, Peter Naredi, Ola Nilsson, Marcela Davila Lopez, Ulrika Stierner, Lars Ny, Jonas A. Nilsson. Melanoma patient-derived xenografts accurately models the disease and develop fast enough to guide treatment decisions. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr B38.
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.MEL2014-B38
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2015
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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