Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies

Depreeuw, Jeroen; Hermans, Els; Schrauwen, Stefanie; Annibali, Daniela; Coenegrachts, Lieve; Thomas, Debby; Luyckx, Mathieu; Gutierrez-Roelens, Ilse; Debruyne, David; Konings, Katrien; Moerman, Philippe; Vergote, Ignace; Lambrechts, Diether; Amant, Frédéric

doi:10.1016/j.ygyno.2015.07.104

Cited by 51 publications

(51 citation statements)

References 27 publications

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“…For aggressive tumors that cannot be ablated such as aggressive lung cancer, CT-guided percutaneous lung puncture has become the main means of diagnosis, because it can obtain adequate cells or tissue samples, and has high diagnostic accuracy (3,12). Furthermore, it has been proven that the pathological immunohistochemistry and expression of biological markers between biopsy samples and surgical samples are well correlated (7 ,13–15 ). In the past 10 years, multi-gene detection analysis has been done using biopsy samples, which provide important gene phenotyping decision-making evidence for the use of treatment drugs such as molecular-targeted drugs (14–17).…”

Section: Discussionmentioning

confidence: 99%

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

Zhuang

Zhu²,

Wang

et al. 2017

Braz J Med Biol Res

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This study aimed to investigate the feasibility of the establishment of a human cancer xenograft model using samples from computed tomography (CT)-guided percutaneous biopsy. Fresh tumor tissues obtained from 10 cancer patients by CT-guided percutaneous biopsy were subcutaneously inoculated into NOD-Prkdcem26Il2rgem26Nju (NCG) mice to establish human patient-derived tumor xenograft (PDTX) models. The formation of first and second generation xenografts was observed, and tumor volume was recorded over time. Tumor tissue consistency between the PDTX model and primary tumors in patients was compared using H&E staining and immunohistochemistry. Pharmacodynamic tests of clinically used chemotherapeutic drugs were conducted on second generation xenografts, and their effects on tumor growth and body weight were observed. CT-guided percutaneous biopsy samples were successfully collected from 10 patients with advanced cancers. The PDTX model was established in mice using tumor samples obtained from 4 cancer patients, including one small cell carcinoma sample, two adenocarcinoma samples, and one squamous cell carcinoma sample. The success rate was 40%. The obtained PDTX model maintained a degree of differentiation, and morphological and structural characteristics were similar to primary tumors. The pharmacodynamic test of chemotherapeutic drugs in the PDTX model revealed a therapeutic effect on tumor growth, as expected. CT-guided percutaneous biopsy samples can be effectively used to establish a PDTX model, and test these chemotherapy regimens.

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Section: Discussionmentioning

confidence: 99%

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

Zhuang

Zhu²,

Wang

et al. 2017

Braz J Med Biol Res

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“…Next, human stroma in mice is replaced by murine stroma over different generations. This has been shown for different types of tumours, but also more specifically for EC [33]. Both immunological and stromal cells are part of the tumour microenvironment, and it is known that they are implicated in cancer progression and metastasis [70].…”

Section: Pdx-related Challengesmentioning

confidence: 99%

“…Later on, Depreeuw et al [33] developed and fully characterized a panel of 24 subcutaneous EC PDX models that includes more frequent histologic and genetic subtypes of EC. The authors demonstrated that EC PDX models can be successfully established from both primary, metastatic, and recurrent endometrioid EC and non-endometrioid EC tumours, with an overall engraftment rate of 60%.…”

Section: Endometrial Cancer Pdx Modelsmentioning

confidence: 99%

“…Similarly, Dupreeuw et al [33] tested the efficacy of NVP-BEZ235 (a dual pan-PI3K/mTOR inhibitor) and AZD6244 (an MEK1/2 inhibitor) in a PDX model harbouring a high-grade recurrent endometrioid carcinoma carrying PTEN, PIK3CA, and KRAS mutations. They showed that the treatment as a single therapy significantly reduced tumour growth compared to the control group.…”

Section: Endometrial Cancer Pdx Modelsmentioning

confidence: 99%

“…However, several SCNAs observed in primary tumours disappear in PDX models and SCNAs acquired by PDXs differ from primary tumours [72]. Other studies suggest that, although there is indeed engraftment-associated selection, the majority of changes do not occur in oncogenic drivers and are therefore not affecting intra-tumour heterogeneity [33,68,73]. …”

Section: Pdx-related Challengesmentioning

confidence: 99%

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Patient-Derived Xenograft Models for Endometrial Cancer Research

Moiola

Lopez-Gil

Cabrera

et al. 2018

IJMS

Self Cite

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Endometrial cancer (EC) is the most common malignancy of the genital tract among women in developed countries. Recently, a molecular classification of EC has been performed providing a system that, in conjunction with histological observations, reliably improves EC classification and enhances patient management. Patient-derived xenograft models (PDX) represent nowadays a promising tool for translational research, since they closely resemble patient tumour features and retain molecular and histological features. In EC, PDX models have already been used, mainly as an individualized approach to evaluate the efficacy of novel therapies and to identify treatment-response biomarkers; however, their uses in more global or holistic approaches are still missing. As a collaborative effort within the ENITEC network, here we describe one of the most extensive EC PDX cohorts developed from primary tumour and metastasis covering all EC subtypes. Our models are histologically and molecularly characterized and represent an excellent reservoir of EC tumour samples for translational research. This review compiles the information on current methods of EC PDX generation and their utility and provides new perspectives for the exploitation of these valuable tools in order to increase the success ratio for translating results to clinical practice.

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Generation and Integrated Analysis of Advanced Patient‐Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer

et al. 2022

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Clinical management of endometrial cancer (EC) is handicapped by the limited availability of second line treatments and bona fide molecular biomarkers to predict recurrence. These limitations have hampered the treatment of these patients, whose survival rates have not improved over the last four decades. The advent of coordinated studies such as The Cancer Genome Atlas Uterine Corpus Endometrial Carcinoma (TCGA_UCEC) has partially solved this issue, but the lack of proper experimental systems still represents a bottleneck that precludes translational studies from successful clinical testing in EC patients. Within this context, the first study reporting the generation of a collection of endometrioid-EC-patient-derived orthoxenograft (PDOX) mouse models is presented that is believed to overcome these experimental constraints and pave the way toward state-of-the-art precision medicine in EC. The collection of primary tumors and derived PDOXs is characterized through an integrative approach based on transcriptomics, mutational profiles, and morphological analysis; and it is demonstrated that EC tumors engrafted in the mouse uterus retain the main molecular and morphological features from analogous tumor donors. Finally, the molecular properties of these tumors are harnessed to assess the therapeutic potential of trastuzumab, a human epidermal growth factor receptor 2 (HER2) inhibitor with growing interest in EC, using patient-derived organotypic multicellular tumor spheroids and in vivo experiments.

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Characterization of patient-derived tumor xenograft models of endometrial cancer for preclinical evaluation of targeted therapies

Cited by 51 publications

References 27 publications

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

Establishment of patient-derived tumor xenograft (PDTX) models using samples from CT-guided percutaneous biopsy

Patient-Derived Xenograft Models for Endometrial Cancer Research

Generation and Integrated Analysis of Advanced Patient‐Derived Orthoxenograft Models (PDOX) for the Rational Assessment of Targeted Therapies in Endometrial Cancer

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