Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer

Lawrence, Mitchell G.; Pook, David; Wang, Hong; Porter, Laura H.; Frydenberg, Mark; Kourambas, John; Appu, Sree; Poole, Christine; Beardsley, Emma Kate; Ryan, Andrew; Norden, Sam; Papargiris, Melissa; Risbridger, Gail P.; Taylor, Renea A.

doi:10.1002/pros.23039

Cited by 34 publications

(23 citation statements)

References 22 publications

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“…In the case of one CRC study, approximately 70% of patient samples grafts developed a PDX (22). Anecdotal practices, speculative factors and limited experimental findings in other tumor types support the notion that engraftment rates are affected by several factors, including tumor type, tissue source, cancer stage, tumor grade, tumor molecular characteristics, acquisition strategy, exposure to prior radiation or systemic chemotherapy, and technical manipulations during grafting (such as time to implantation) (30–33). In this study, we established a large cohort of PDX models derived from both surgical and biopsy specimens to systematically examine whether these factors effect engraftment in PDX models.…”

Section: Introductionmentioning

confidence: 91%

Modeling of Patient-Derived Xenografts in Colorectal Cancer

Katsiampoura

Raghav

Jiang

et al. 2017

Molecular Cancer Therapeutics

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Developing realistic preclinical models using clinical samples that mirror complex tumor biology and behavior are vital to advancing cancer research. While cell-line cultures have been helpful in generating preclinical data, the genetic divergence between these and corresponding primary tumors has limited clinical translation. Conversely, patient derived xenografts (PDXs) in colorectal cancer (CRC) are highly representative of the genetic and phenotypic heterogeneity in the original tumor. Coupled with high-throughput analyses and bioinformatics, these PDXs represent robust preclinical tools for biomarkers, therapeutic target and drug discovery. Successful PDX engraftment is hypothesized to be related to a series of anecdotal variables namely, tissue source, cancer stage, tumor grade, acquisition strategy, time to implantation, exposure to prior systemic therapy, and genomic heterogeneity of tumors. Although these factors at large can influence practices and patterns related to xenotransplantation, their relative significance in determining the success of establishing PDXs is uncertain. Accordingly, we systematically examined the predictive ability of these factors in establishing PDXs using 90 CRC patient specimens that were subcutaneously implanted into immunodeficient mice. Fifty (56%) PDXs were successfully established. Multivariate analyses showed tissue acquisition strategy [surgery 72.0% (95% confidence interval (CI): 58.2–82.6) vs. biopsy 35% (95%CI: 22.1–50.6%)] to be the key determinant for successful PDX engraftment. These findings contrast with current empiricism in generating PDXs and can serve to simplify or liberalize PDX modelling protocols. Better understanding the relative impact of these factors on efficiency of PDX formation will allow for pervasive integration of these models in care of CRC patients.

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Section: Introductionmentioning

confidence: 91%

Modeling of Patient-Derived Xenografts in Colorectal Cancer

Katsiampoura

Raghav

Jiang

et al. 2017

Molecular Cancer Therapeutics

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“…Therefore, the variation observed in the cancer patient population may not be recapitulated faithfully in PDX models due to this selective engraftment rate [34]. Clinically aggressive tumors with many proliferative cancer cells, have the highest engraftment rate [49,50]. …”

Section: Patient-derived Xenograftsmentioning

confidence: 99%

Ex Vivo Tumor Culture Systems for Functional Drug Testing and Therapy Response Prediction

et al. 2017

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Optimal patient stratification is of utmost importance in the era of personalized medicine. Prediction of individual treatment responses by functional ex vivo assays requires model systems derived from viable tumor samples, which should closely resemble in vivo tumor characteristics and microenvironment. This review discusses a broad spectrum of model systems, ranging from classic 2D monolayer culture techniques to more experimental ‘cancer-on-chip’ procedures. We mainly focus on organotypic tumor slices that take tumor heterogeneity and tumor–stromal interactions into account. These 3D model systems can be exploited for patient selection as well as for fundamental research. Selection of the right model system for each specific research endeavor is crucial and requires careful balancing of the pros and cons of each technology.

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“…The sources of tissue vary considerably with this subsequently affecting the quality of the specimens used for engraftment. However, even the poor specimens obtained at TURP can be grafted sub-renally with moderate success [23]. Dr. Robert Vessella's group at the University of Washington was one of the first to establish serially transplantable PDX models from prostate cancer metastases, namely the LuCaP series [24].…”

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confidence: 99%

Patient-Derived Prostate Cancer: from Basic Science to the Clinic

Risbridger

Taylor

2016

HORM CANC

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Systems that model cancer form the backbone of research discovery, and their accuracy and validity are a key determinant to ensure successful translation. In many tumour types, patient-derived specimens are an important model of choice for pre-clinical drug development. In this review, we consider why this has been such a challenge for prostate cancer, resulting in relatively few patient-derived xenografts (PDXs) of prostatic tumours compared to breast cancers, for example. Nevertheless, with only a few patient specimens and PDXs, we exemplify in three vignettes how important new clinical insights were obtained resulting in benefit for future men with prostate cancer.

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Establishment of primary patient-derived xenografts of palliative TURP specimens to study castrate-resistant prostate cancer

Cited by 34 publications

References 22 publications

Modeling of Patient-Derived Xenografts in Colorectal Cancer

Modeling of Patient-Derived Xenografts in Colorectal Cancer

Ex Vivo Tumor Culture Systems for Functional Drug Testing and Therapy Response Prediction

Patient-Derived Prostate Cancer: from Basic Science to the Clinic

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