Patient Derived Ex-Vivo Cancer Models in Drug Development, Personalized Medicine, and Radiotherapy

Zitter, Ryan; Chugh, Rishi Man; Saha, Subhrajit

doi:10.3390/cancers14123006

Cited by 9 publications

(3 citation statements)

References 118 publications

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“…The molecular biology of sarcomas is poorly understood, especially the interplay among signaling pathways, as well as the epigenetic modifications and regulatory RNA sequences. Patient-derived 3D sarcoma models could be useful to recapitulate the three-dimensional structure of these neoplasms, clarifying the complex crosstalk between tumor cells and their microenvironment, and contributing to personalized medicine development [7,53].…”

Section: Established Cancer-derived Cell Linesmentioning

confidence: 99%

Preclinical Models of Visceral Sarcomas

Costa,

Gozzellino,

Nannini

et al. 2023

Biomolecules

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Visceral sarcomas are a rare malignant subgroup of soft tissue sarcomas (STSs). STSs, accounting for 1% of all adult tumors, are derived from mesenchymal tissues and exhibit a wide heterogeneity. Their rarity and the high number of histotypes hinder the understanding of tumor development mechanisms and negatively influence clinical outcomes and treatment approaches. Although some STSs (~20%) have identifiable genetic markers, as specific mutations or translocations, most are characterized by complex genomic profiles. Thus, identification of new therapeutic targets and development of personalized therapies are urgent clinical needs. Although cell lines are useful for preclinical investigations, more reliable preclinical models are required to develop and test new potential therapies. Here, we provide an overview of the available in vitro and in vivo models of visceral sarcomas, whose gene signatures are still not well characterized, to highlight current challenges and provide insights for future studies.

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Section: Established Cancer-derived Cell Linesmentioning

confidence: 99%

Preclinical Models of Visceral Sarcomas

Costa,

Gozzellino,

Nannini

et al. 2023

Biomolecules

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“…Up to 50% of these failures are due to lack of clinical efficacy, which can be interpreted as a lack of pre-clinical models that accurately reflect in vivo response [ 9 , 10 ]. Given its ability to mimic the 3D multicellular architecture of human disease, the ex vivo patient-derived explant (PDE) culture technique has recently emerged as a powerful preclinical platform for cancer research [ 11 ]. PDEs are typically small (1–3 mm in diameter) pieces of fresh tumour that are cultured without disintegration into the tissue’s individual cellular components.…”

Section: Introductionmentioning

confidence: 99%

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

van der Woude,

Phan,

Kenwright

et al. 2024

PLoS ONE

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Incidence of endometrial cancer (EC) is rising in the developed world. The current standard of care, hysterectomy, is often infeasible for younger patients and those with high body mass index. There are limited non-surgical treatment options and a lack of biologically relevant research models to investigate novel alternatives to surgery for EC. The aim of the present study was to develop a long-term, patient-derived explant (PDE) model of early-stage EC and demonstrate its use for investigating predictive biomarkers for a current non-surgical treatment option, the levonorgestrel intra-uterine system (LNG-IUS). Fresh tumour specimens were obtained from patients with early-stage endometrioid EC. Tumours were cut into explants, cultured on media-soaked gelatin sponges for up to 21 days and treated with LNG. Formalin-fixed, paraffin embedded (FFPE) blocks were generated for each explant after 21 days in culture. Tumour architecture and integrity were assessed by haematoxylin and eosin (H&E) and immunohistochemistry (IHC). IHC was additionally performed for the expression of five candidate biomarkers of LNG resistance. The developed ex vivo PDE model is capable of culturing explants from early-stage EC tumours long-term (21 Days). This model can complement existing models and may serve as a tool to validate results obtained in higher-throughput in vitro studies. Our study provides the foundation to validate the extent to which EC PDEs reflect patient response in future research.

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“…Although 2D monolayer cancer-derived cells are often used in imaging assays (31), there are conflicting reports of their limited expansion potential. Jeppesen et al conducted a comparative study of colorectal cancer cell extraction and cultivation procedures as monolayer cultures (32) and concluded that trypsin was the best method to digest the tissue.…”

Section: Introductionmentioning

confidence: 99%

Recent developments in the production of 2D- and 3D colon and stomach adenocarcinomas primary cell models

Tokarchuck¹,

Mushii²,

Dreus³

et al. 2023

Preprint

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Gastric and colorectal cancer models are essential for the advancement of precision medicine discovery and development. 2D attached monolayer, spheroid and organoid approaches have all been used in the formation of biobanks containing primary patient-derived cells. Here, we report an assessment of those procedures for a panel of nine patient-derived adenocarcinoma samples, along with the most applicable method for the bio-banking of these cell types. A live cell biobank of tumour specimens would facilitate drug discovery laboratories to evaluate drugs on the population of cell cultures, prior to the clinical phase.

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Patient Derived Ex-Vivo Cancer Models in Drug Development, Personalized Medicine, and Radiotherapy

Cited by 9 publications

References 118 publications

Preclinical Models of Visceral Sarcomas

Preclinical Models of Visceral Sarcomas

Development of a long term, ex vivo, patient-derived explant model of endometrial cancer

Recent developments in the production of 2D- and 3D colon and stomach adenocarcinomas primary cell models

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