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


ABSTRACT: 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.

SUBMITTER: Krepler C 

PROVIDER: S-EPMC5726788 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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

Krepler Clemens C   Sproesser Katrin K   Brafford Patricia P   Beqiri Marilda M   Garman Bradley B   Xiao Min M   Shannan Batool B   Watters Andrea A   Perego Michela M   Zhang Gao G   Vultur Adina A   Yin Xiangfan X   Liu Qin Q   Anastopoulos Ioannis N IN   Wubbenhorst Bradley B   Wilson Melissa A MA   Xu Wei W   Karakousis Giorgos G   Feldman Michael M   Xu Xiaowei X   Amaravadi Ravi R   Gangadhar Tara C TC   Elder David E DE   Haydu Lauren E LE   Wargo Jennifer A JA   Davies Michael A MA   Lu Yiling Y   Mills Gordon B GB   Frederick Dennie T DT   Barzily-Rokni Michal M   Flaherty Keith T KT   Hoon Dave S DS   Guarino Michael M   Bennett Joseph J JJ   Ryan Randall W RW   Petrelli Nicholas J NJ   Shields Carol L CL   Terai Mizue M   Sato Takami T   Aplin Andrew E AE   Roesch Alexander A   Darr David D   Angus Steve S   Kumar Rakesh R   Halilovic Ensar E   Caponigro Giordano G   Jeay Sebastien S   Wuerthner Jens J   Walter Annette A   Ocker Matthias M   Boxer Matthew B MB   Schuchter Lynn L   Nathanson Katherine L KL   Herlyn Meenhard M  

Cell reports 20171101 7


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  ...[more]

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