High Fidelity Patient-Derived Xenografts for Accelerating Prostate Cancer Discovery and Drug Development

被引：297

作者：

Lin, Dong ^{[1
,2
]}

Wyatt, Alexander W. ^{[1
,2
]}

Xue, Hui

Wang, Yuwei

Dong, Xin

Haegert, Anne ^{[1
,2
]}

Wu, Rebecca

Brahmbhatt, Sonal ^{[1
,2
]}

Mo, Fan ^{[1
,2
]}

Jong, Lina ^{[1
,2
]}

Bell, Robert H. ^{[1
,2
]}

Anderson, Shawn ^{[1
,2
]}

Hurtado-Coll, Antonio ^{[1
,2
]}

Fazli, Ladan ^{[1
,2
]}

Sharma, Manju ^{[1
,2
]}

Beltran, Himisha ^{[4
]}

Rubin, Mark ^{[5
]}

Cox, Michael ^{[1
,2
]}

Gout, Peter W.

Morris, James ^{[3
]}

Goldenberg, Larry ^{[2
]}

Volik, Stanislav V. ^{[1
,2
]}

Gleave, Martin E. ^{[1
,2
]}

Collins, Colin C. ^{[1
,2
]}

Wang, Yuzhuo ^{[1
,2
]}

机构：

[1] Univ British Columbia, Fac Med, Vancouver Prostate Ctr, Vancouver, BC, Canada

[2] Univ British Columbia, Fac Med, Dept Urol Sci, Vancouver, BC, Canada

[3] BC Canc Agcy, Dept Radiat Oncol, Vancouver, BC VZ5 1L3, Canada

[4] Weill Cornell Med Coll, Weill Cornell Canc Ctr, Dept Med, New York, NY USA

[5] Weill Cornell Med Coll, Weill Cornell Canc Ctr, Dept Pathol & Lab Med, New York, NY USA

来源：

CANCER RESEARCH | 2014年 / 74卷 / 04期

基金：

加拿大健康研究院;

关键词：

SMALL-CELL CARCINOMA; GENE REARRANGEMENTS; LUNG CANCERS; MODEL; CASTRATION; PROGRESSION; METASTASIS; GENOME; COMMON; MOUSE;

D O I：

10.1158/0008-5472.CAN-13-2921-T

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Standardized and reproducible preclinical models that recapitulate the dynamics of prostate cancer are urgently needed. We established a bank of transplantable patient-derived prostate cancer xenografts that capture the biologic and molecular heterogeneity currently confounding prognostication and therapy development. Xenografts preserved the histopathology, genome architecture, and global gene expression of donor tumors. Moreover, their aggressiveness matched patient observations, and their response to androgen withdrawal correlated with tumor subtype. The panel includes the first xenografts generated from needle biopsy tissue obtained at diagnosis. This advance was exploited to generate independent xenografts from different sites of a primary site, enabling functional dissection of tumor heterogeneity. Prolonged exposure of adenocarcinoma xenografts to androgen withdrawal led to castration-resistant prostate cancer, including the first-in-field model of complete transdifferentiation into lethal neuroendocrine prostate cancer. Further analysis of this model supports the hypothesis that neuroendocrine prostate cancer can evolve directly from adenocarcinoma via an adaptive response and yielded a set of genes potentially involved in neuroendocrine transdifferentiation. We predict that these next-generation models will be transformative for advancing mechanistic understanding of disease progression, response to therapy, and personalized oncology. (C)2013 AACR.

引用

页码：1272 / 1283

页数：12

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