5 years ago

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma

A Comprehensive Patient-Derived Xenograft Collection Representing the Heterogeneity of Melanoma
Ensar Halilovic, Matthew B. Boxer, Dave S. Hoon, Gordon B. Mills, Ioannis N. Anastopoulos, Wei Xu, Melissa A. Wilson, Bradley Garman, Steve Angus, Sebastien Jeay, Katherine L. Nathanson, Ravi Amaravadi, Annette Walter, Mizue Terai, Marilda Beqiri, Tara C. Gangadhar, Dennie T. Frederick, Xiaowei Xu, Michal Barzily-Rokni, Gao Zhang, Giordano Caponigro, Andrew E. Aplin, Michela Perego, Katrin Sproesser, Jens Wuerthner, Jennifer A. Wargo, Alexander Roesch, Min Xiao, Adina Vultur, David Darr, Lauren E. Haydu, Andrea Watters, Patricia Brafford, Rakesh Kumar, Carol L. Shields, Keith T. Flaherty, David E. Elder, Bradley Wubbenhorst, Clemens Krepler, Meenhard Herlyn, Qin Liu, Takami Sato, Giorgos Karakousis, Matthias Ocker, Yiling Lu, Nicholas J. Petrelli, Michael A. Davies, Lynn Schuchter, Michael Feldman, Xiangfan Yin, Batool Shannan, Randall W. Ryan, Joseph J. Bennett, Michael Guarino


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.

Publisher URL: http://www.cell.com/cell-reports/fulltext/S2211-1247(17)31453-5

DOI: 10.1016/j.celrep.2017.10.021

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