Endometrial Cancer Patient-Derived Xenograft Models: A Systematic Review

Tanaka, Tomohito; Nishie, Ruri; Ueda, Satoshi; Miyamoto, Shunsuke; Hashida, Sousuke; Konishi, Hiromi; Terada, Shinichi; Kogata, Yuhei; Sasaki, Hiroshi; Tsunetoh, Satoshi; Taniguchi, Kohei; Komura, Kazumasa; Ohmichi, Masahide

doi:10.3390/jcm11092606

Cited by 8 publications

(11 citation statements)

References 51 publications

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“…Compared with the in vitro tumor model, the PDX model can better maintain the histopathological, genetic, and phenotypic characteristics of the tumor tissue, leading to enhance the prediction of the drug response (9,17,18). In recent years, a large number of PDX models have been established in various tumors, including gastric cancer (11,16,19), colorectal cancer (20), lung cancer (21), cervical cancer (22), etc. The PDX models have gradually become an effective tool for tumor biology research and anti-tumor drugs' efficacy evaluation.…”

Section: Discussionmentioning

confidence: 99%

Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study

Chen²,

Lü³

et al. 2022

Front. Oncol.

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BackgroundPatient-derived xenograft (PDX) models have shown a great efficiency in preclinical and translational applications. Gastrointestinal (GI) tumors have a strong heterogeneity, and the engraftment rate of PDX models remarkably vary. However, the clinicopathological and molecular characteristics affecting the engraftment rate still remain elusive.MethodsA total of 312 fresh tumor tissue samples from patients with GI cancer were implanted into immunodeficient mice. The median follow-up time of patients was 37 months. Patients’ characteristics were compared in terms of PDX growth and overall survival. PDX models of 3-6 generations were used for drug evaluation.ResultsIn total, 171 (54.8%, 171/312) PDX models were established, including 85 PDX models of colorectal cancer, 21 PDX models of esophageal cancer, and 65 PDX models of gastric cancer. Other than tumor site, histology, differentiation degree, and serum alpha-fetoprotein (AFP) level, no significant differences were found between transplantation of xenografts and patients’ characteristics. For patients who had undergone neoadjuvant therapy, the incidence of tumor formation was higher in those with progressive disease (PD) or stable disease (SD). In gastric cancer, the results showed a higher transplantation rate in deficient mismatch repair (dMMR) tumors, and Ki-67 could be an important factor affecting the engraftment rate. The gene mutation status of RAS and BRAF, two important molecular markers in colorectal cancer, showed a high degree of consistency between patients’ tumors and PDXs. However, no significant effects of these two mutations on PDX engraftment rate were observed. More importantly, in this study although KRAS mutations were detected in two clinical cases, evident tumor inhibition was still observed after cetuximab treatment in both PDX models and patients.ConclusionA large-scale PDX model including 171 cases was successfully established for GI tumors in our center. The relationship between clinicopathological and molecular features and engraftment rates were clarified. Furthermore, this resource provides us with profound insights into tumor heterogeneity, making these models valuable for PDX-guided treatment decisions, and offering the PDX model as a great tool for personalized treatment and translation research.

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Section: Discussionmentioning

confidence: 99%

Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study

Chen²,

Lü³

et al. 2022

Front. Oncol.

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“…As HCI-EC-23 is an adherent cell line, it is more easily amenable to screening efforts and genetic manipulation than PDX models due to the large numbers of cells and conditions required. Although the power of PDX models to recapitulate tumor heterogeneity is clear, the hormonal aspects of these models are often less clear and are largely only assessed by hormone-receptor positivity [30][31][32][33] . We believe that HCI-EC-23 is uniquely situated to vastly improve the quality of research regarding the molecular aspects of hormonally driven endometrial cancer by providing another well-characterized cell line model for investigators to utilize.…”

Section: Discussionmentioning

confidence: 99%

Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line

Rush

Blanchard

Polaski

et al. 2022

Sci Rep

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Most endometrial cancers express the hormone receptor estrogen receptor alpha (ER) and are driven by excess estrogen signaling. However, evaluation of the estrogen response in endometrial cancer cells has been limited by the availability of hormonally responsive in vitro models, with one cell line, Ishikawa, being used in most studies. Here, we describe a novel, adherent endometrioid endometrial cancer (EEC) cell line model, HCI-EC-23. We show that HCI-EC-23 retains ER expression and that ER functionally responds to estrogen induction over a range of passages. We also demonstrate that this cell line retains paradoxical activation of ER by tamoxifen, which is also observed in Ishikawa and is consistent with clinical data. The mutational landscape shows that HCI-EC-23 is mutated at many of the commonly altered genes in EEC, has relatively few copy-number alterations, and is microsatellite instable high (MSI-high). In vitro proliferation of HCI-EC-23 is strongly reduced upon combination estrogen and progesterone treatment. HCI-EC-23 exhibits strong estrogen dependence for tumor growth in vivo and tumor size is reduced by combination estrogen and progesterone treatment. Molecular characterization of estrogen induction in HCI-EC-23 revealed hundreds of estrogen-responsive genes that significantly overlapped with those regulated in Ishikawa. Analysis of ER genome binding identified similar patterns in HCI-EC-23 and Ishikawa, although ER exhibited more bound sites in Ishikawa. This study demonstrates that HCI-EC-23 is an estrogen- and progesterone-responsive cell line model that can be used to study the hormonal aspects of endometrial cancer.

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“…Humanized mouse models, which are engrafted with functional human cells and tissues, including human peripheral blood mononuclear cells (PBMCs), CD34+ human hematopoietic cells, or bone marrow-liver-thymus (BLT) tissue, are widely used for the biomedical research [ 66 ]. The NSG, NCG, and NOG mouse strains are suitable for creating humanized mice because they lack T-cell subsets, B cells, and natural killer (NK) cells.…”

Section: Classification Of Animal Modelsmentioning

confidence: 99%

Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models

Chen¹,

Zheng

Zhang

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Non-small-cell lung cancer (NSCLC) is known as one of the most lethal cancers, causing more than 1 million deaths annually worldwide. Therefore, the development of novel therapeutic drugs for NSCLC has become an urgent need. Herein, various mouse models provide great convenience not only for researchers but also for the development of antitumor drug. Meanwhile, TCM, as a valuable and largely untapped resource pool for modern medicine, provides research resources for the treatment of various diseases. Until now, cell-derived xenograft (CDX) model, patient-derived xenograft (PDX) model, syngeneic model, orthotopic model, humanized mouse model (HIS), and genetically engineered mouse models (GEMMs) have been reported in TCM evaluation. This review shows the role and current status of kinds of mouse models in antitumor research and summarizes the application progress of TCM including extracts, formulas, and isolated single molecules for NSCLC therapy in various mouse models; more importantly, it provides a theoretical exploration of what kind of mouse models is ideal for TCM efficacy evaluation in future. However, there are still huge challenges and limitations in the development of mouse models specifically for the TCM research, and none of the available models are perfectly matching the characteristics of TCM, which suppress the tumor growth through various mechanisms, especially by regulating immune function. Nevertheless, with fully functional immune system existing in syngeneic model and humanized mouse model (HIS), it is still suggested that these two models are more suitable for development of TCM especially for TCM extracts or formulas. Moreover, continued efforts are needed to generate more reliable mouse models to test TCM formulas in future research.

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Endometrial Cancer Patient-Derived Xenograft Models: A Systematic Review

Cited by 8 publications

References 51 publications

Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study

Patient-derived xenograft models for gastrointestinal tumors: A single-center retrospective study

Characterization of HCI-EC-23 a novel estrogen- and progesterone-responsive endometrial cancer cell line

Research Status of Mouse Models for Non-Small-Cell Lung Cancer (NSCLC) and Antitumor Therapy of Traditional Chinese Medicine (TCM) in Mouse Models

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