A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma
Autor: | Michael J. Guarino, Min Xiao, Giorgos C. Karakousis, Michael A. Davies, Andrea Watters, Ensar Halilovic, Gao Zhang, Alexander Roesch, Lauren E. Haydu, Giordano Caponigro, Keith T. Flaherty, Clemens Krepler, Katrin Sproesser, Gordon B. Mills, Sébastien Jeay, Andrew E. Aplin, Lynn M. Schuchter, Nicholas J. Petrelli, Joseph J. Bennett, Adina Vultur, David E. Elder, Meenhard Herlyn, Ravi K. Amaravadi, Michael Feldman, Xiangfan Yin, Melissa Wilson, Tara C. Gangadhar, Rakesh Kumar, Michela Perego, Carol L. Shields, Katherine L. Nathanson, Marilda Beqiri, Jennifer A. Wargo, Matthias Ocker, Takami Sato, Qin Liu, Michal Barzily-Rokni, Batool Shannan, Ioannis N. Anastopoulos, Dennie T. Frederick, Bradley Garman, Xiaowei Xu, Dave S.B. Hoon, Mizue Terai, Randall W Ryan, Yiling Lu, Bradley Wubbenhorst, Patricia Brafford, Matthew B. Boxer, Annette O. Walter, Wei Xu, Jens Wuerthner, Steve Angus, David B. Darr |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
medicine.medical_treatment Medizin Biology Article General Biochemistry Genetics and Molecular Biology Targeted therapy Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Humans lcsh:QH301-705.5 Melanoma Cells Cultured Tumor xenograft Advanced melanoma Cancer medicine.disease Xenograft Model Antitumor Assays Immune checkpoint Blockade 030104 developmental biology lcsh:Biology (General) 030220 oncology & carcinogenesis Cancer research Heterografts Brain metastasis |
Zdroj: | Cell Reports, Vol 21, Iss 7, Pp 1953-1967 (2017) |
ISSN: | 2211-1247 |
DOI: | 10.1016/j.celrep.2017.10.021 |
Popis: | Summary: Therapy of advanced melanoma is changing dramatically. Following mutational and biological subclassification of this heterogeneous cancer, several targeted and immune therapies were approved and increased survival significantly. To facilitate further advancements through pre-clinical in vivo modeling, we have established 459 patient-derived xenografts (PDX) and live tissue samples from 384 patients representing the full spectrum of clinical, therapeutic, mutational, and biological heterogeneity of melanoma. PDX have been characterized using targeted sequencing and protein arrays and are clinically annotated. This exhaustive live tissue resource includes PDX from 57 samples resistant to targeted therapy, 61 samples from responders and non-responders to immune checkpoint blockade, and 31 samples from brain metastasis. Uveal, mucosal, and acral subtypes are represented as well. We show examples of pre-clinical trials that highlight how the PDX collection can be used to develop and optimize precision therapies, biomarkers of response, and the targeting of rare genetic subgroups. : Krepler et al. have established a collection of melanoma patient-derived xenografts (PDX). Melanoma is a very heterogeneous cancer, and this large collection includes even rare subtypes and genetic aberrations in sufficient numbers. Multiple PDX from therapy-resistant patients are characterized and tested in pre-clinical trials for second line therapies. Keywords: melanoma, patient-derived xenografts, targeted therapy, immune checkpoint blockade, melanoma brain metastasis, in vivo models, BRAF inhibitor resistance, ERK inhibitor, MDM2 inhibitor, PI3K beta inhibitor |
Databáze: | OpenAIRE |
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