Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

Templeton, Abby R.; Jeffery, Penny L.; Thomas, Patrick B.; Perera, Mahasha P. J.; Ng, Gary; Calabrese, Alivia R.; Nicholls, Clarissa; Mackenzie, Nathan J.; Wood, Jack; Bray, Laura J.; Vela, Ian; Thompson, Erik W.; Williams, Elizabeth D.

doi:10.3389/fonc.2021.767697

Cited by 20 publications

(23 citation statements)

References 74 publications

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“…Demonstrating that our clinical data mirrors pre-clinical PDE results will provide irrefutable evidence for the use of PDEs in drug and biomarker discovery. It will also support recent studies suggesting PDEs as a platform to directly inform clinical management through precision medicine [ 56 ].…”

Section: Discussionsupporting

confidence: 63%

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Centenera

Vincent

Moldovan

et al. 2022

Cancers

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Prostate cancer is a complex and heterogeneous disease, but a small number of cell lines have dominated basic prostate cancer research, representing a major obstacle in the field of drug and biomarker discovery. A growing lack of confidence in cell lines has seen a shift toward more sophisticated pre-clinical cancer models that incorporate patient-derived tumors as xenografts or explants, to more accurately reflect clinical disease. Not only do these models retain critical features of the original tumor, and account for the molecular diversity and cellular heterogeneity of prostate cancer, but they provide a unique opportunity to conduct research in matched tumor samples. The challenge that accompanies these complex tissue models is increased complexity of analysis. With over 10 years of experience working with patient-derived explants (PDEs) of prostate cancer, this study provides guidance on the PDE method, its limitations, and considerations for addressing the heterogeneity of prostate cancer PDEs that are based on statistical modeling. Using inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) as an example of a drug that induces robust proliferative response, we demonstrate how multi-omics analysis in prostate cancer PDEs is both feasible and essential for identification of key biological pathways, with significant potential for novel drug target and biomarker discovery.

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Section: Discussionsupporting

confidence: 63%

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Centenera

Vincent

Moldovan

et al. 2022

Cancers

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“…However, there appears to be little information on the use of this latter method in precision slicing of EOC, and therefore, further studies are needed to define the golden standard approach. For incubation conditions most studies use 37 °C, 5% CO 2 and 21% oxygen [ 71 , 78 ]. Further details on culture conditions can be found in a focused review by Templeton et al [ 78 ].…”

Section: In Vitro and Ex Vivo Modelsmentioning

confidence: 99%

“…For incubation conditions most studies use 37 °C, 5% CO 2 and 21% oxygen [ 71 , 78 ]. Further details on culture conditions can be found in a focused review by Templeton et al [ 78 ]. Tumor explants cultures can also be combined with adjacent healthy tissue or cell culture, as for example lymphocytes from peripheral blood mononuclear cells (PBMC).…”

Section: In Vitro and Ex Vivo Modelsmentioning

confidence: 99%

“…Endpoint analysis for studies assessing drug response includes either enzymatic digestion followed by evaluation of cell viability or cytotoxicity using the MTT (3-(6)-2,5-diphenyltetrazolium bromide) assay [as in the case of Histoculture drug response assay (HDRA) assay [ 79 ]] or the PDE can be left intact and processed for spatial biomarker analysis [ 78 ]. If the PDE is homogenized, protein and nucleic acids can be extracted and omics data generated.…”

Section: In Vitro and Ex Vivo Modelsmentioning

confidence: 99%

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Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application

Ciucci

Buttarelli

Fagotti

et al. 2022

Cell. Mol. Life Sci.

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Despite many improvements in ovarian cancer diagnosis and treatment, until now, conventional chemotherapy and new biological drugs have not been shown to cure the disease, and the overall prognosis remains poor. Over 90% of ovarian malignancies are categorized as epithelial ovarian cancers (EOC), a collection of different types of neoplasms with distinctive disease biology, response to chemotherapy, and outcome. Advances in our understanding of the histopathology and molecular features of EOC subtypes, as well as the cellular origins of these cancers, have given a boost to the development of clinically relevant experimental models. The overall goal of this review is to provide a comprehensive description of the available preclinical investigational approaches aimed at better characterizing disease development and progression and at identifying new therapeutic strategies. Systems discussed comprise monolayer (2D) and three-dimensional (3D) cultures of established and primary cancer cell lines, organoids and patient-derived explants, animal models, including carcinogen-induced, syngeneic, genetically engineered mouse, xenografts, patient-derived xenografts (PDX), humanized PDX, and the zebrafish and the laying hen models. Recent advances in tumour-on-a-chip platforms are also detailed. The critical analysis of strengths and weaknesses of each experimental model will aid in identifying opportunities to optimize their translational value.

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“…Both low and high tumor grades (Gleason 3-5) have been cultured successfully and remain viable for up to five days ( 3 , 8 , 10 , 11 ). The methodology for PDE cultures and the promise of their preclinical utility has been previously reviewed by others ( 20 , 28 , 29 ) and is only briefly discussed here.…”

Section: Therapeutic Responses In Ex Vivo Pde and Tsmentioning

confidence: 99%

Harnessing the Utility of Ex Vivo Patient Prostate Tissue Slice Cultures

Perez

Nonn

2022

Front. Oncol.

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Patient-derived prostate tissue explant cultures are powerful research tools that offer the potential for personalized medicine. These cultures preserve the local microenvironment of the surrounding stroma but are not without limitations and challenges. There are several methods and processing techniques to culture tissue ex vivo, that include explant tissue chunks and precision-cut tissue slices. Precision-cut tissue slices provide a consistent distribution of nutrients and gases to the explant. Herein we summarize the prostate tissue slice method, its limitations and discuss the utility of this model, to investigate prostate biology and therapeutic treatment responses.

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Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management

Cited by 20 publications

References 74 publications

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Harnessing the Heterogeneity of Prostate Cancer for Target Discovery Using Patient-Derived Explants

Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application

Harnessing the Utility of Ex Vivo Patient Prostate Tissue Slice Cultures

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