Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers

Lan, Tianfeng; Xue, Xindong; Dunmall, Louisa Chard; Miao, Jinxin; Wang, Yaohe

doi:10.18632/aging.202934

Cited by 7 publications

(6 citation statements)

References 158 publications

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“…SHR6390 suppressed tumor cell growth in vitro and suppressed tumor growth in PDX models. [363][364][365] This kind of inhibitor suppressed RB phosphorylation and blocked the cell cycle at G1 in vivo. The combination of SHR6390 with paclitaxel or cisplatin had synergistic action in inhibiting tumor growth in vivo.…”

Section: Egfr Inhibitorsmentioning

confidence: 99%

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Tie

Alu

et al. 2023

Sig Transduct Target Ther

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Head and neck cancer (HNC) is malignant, genetically complex and difficult to treat and is the sixth most frequent cancer, with tobacco, alcohol and human papillomavirus being major risk factors. Based on epigenetic data, HNC is remarkably heterogeneous, and treatment remains challenging. There is a lack of significant improvement in survival and quality of life in patients with HNC. Over half of HNC patients experience locoregional recurrence or distal metastasis despite the current multiple traditional therapeutic strategies and immunotherapy. In addition, resistance to chemotherapy, radiotherapy and some targeted therapies is common. Therefore, it is urgent to explore more effective and tolerable targeted therapies to improve the clinical outcomes of HNC patients. Recent targeted therapy studies have focused on identifying promising biomarkers and developing more effective targeted therapies. A well understanding of the pathogenesis of HNC contributes to learning more about its inner association, which provides novel insight into the development of small molecule inhibitors. In this review, we summarized the vital signaling pathways and discussed the current potential therapeutic targets against critical molecules in HNC, as well as presenting preclinical animal models and ongoing or completed clinical studies about targeted therapy, which may contribute to a more favorable prognosis of HNC. Targeted therapy in combination with other therapies and its limitations were also discussed.

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Section: Egfr Inhibitorsmentioning

confidence: 99%

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Tie

Alu

et al. 2023

Sig Transduct Target Ther

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“…The success rate of PDX models for EC established through subcutaneous transplantation is 13.3%-55.5% [27] and is lower than that of models for other tumors [10]. Three reasons for the failure of subcutaneous PDX model establishment include lymphoproliferative lesion (LPL) replacement, absent tumor growth, and unplanned death or host infection [28].…”

Section: Construction and Optimization Of Pdx Modelsmentioning

confidence: 99%

Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer

Liang

Cheng

et al. 2023

Preprint

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Esophageal cancer (EC) is the tenth most common cancer worldwide and has high morbidity and mortality. Its main subtypes include esophageal squamous cell carcinoma and esophageal adenocarcinoma, which are usually diagnosed in their late stages. The biological defects and inability of preclinical models to summarize completely the etiology of multiple factors, the complexity of the tumor microenvironment, and the genetic heterogeneity of tumors severely limit the clinical treatment of EC. Patient-derived models of EC not only retain the tissue structure, cell morphology, and differentiation characteristics of the original tumor, they also retain tumor heterogeneity. Therefore, compared with other preclinical models, they can better predict the efficacy of candidate drugs, explore novel biomarkers, combine with clinical trials, and effectively improve patient prognosis. This review discusses the methods and animals used to establish patient-derived models, especially patient-derived xenograft models. It also discusses their advantages, applications, and limitations as preclinical experimental research tools to provide an important reference for the precise personalized treatment of EC and improve the prognosis of patients.

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“…To genetically inactivate IL2RG in the hamster, we employed the CRISPR/cas9 system with single guide RNAs (sgRNAs) designed to target its exon 1. Among the produced hamster lines carrying different insertions and deletions (indels) in exon 1, lines with frameshift mutations causing multiple premature stop codons in IL2RG were chosen for the establishment of IL2RG KO hamster colonies and used to produce experimental animals [ 38 , 53 ]. Lymphocyte-specific gene expression analyses in the spleen showed that IL2RG KO hamsters present severe defects in lymphocyte development which are characterized by a greatly reduced number of CD4 + T cells and barely detectable CD8 + T cells, B cells, and NK cells, mimicking many aspects of human XSCID immunodeficiency.…”

Section: Kcnq1 Tp53 and Il2rg...mentioning

confidence: 99%

“…The use of immunodeficient animals, either with IL2RG-deficiency alone or in combination with other immunodeficiencies such as RAG2-deficiency, as hosts to produce PDX models relies on their incapability of mounting immune rejections to human tissues, therefore allowing them to be xenografted in the animal hosts. Compared to in vitro cultured tumor-derived cell lines where in vitro adaptation takes place which may change the physiology of tumors, the PDX models better recapitulate the tumor biology in vivo [ 53 ]. Il2rg KO mice have been widely used as hosts for producing PDX models [ 54 ].…”

Section: Kcnq1 Tp53 and Il2rg...mentioning

confidence: 99%

Golden Syrian Hamster Models for Cancer Research

Wang

Cormier

2022

Cells

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The golden Syrian hamster (Mesocricetus auratus) has long been a valuable rodent model of human diseases, especially infectious and metabolic diseases. Hamsters have also been valuable models of several chemically induced cancers such as the DMBA-induced oral cheek pouch cancer model. Recently, with the application of CRISPR/Cas9 genetic engineering technology, hamsters can now be gene targeted as readily as mouse models. This review describes the phenotypes of three gene-targeted knockout (KO) hamster cancer models, TP53, KCNQ1, and IL2RG. Notably, these hamster models demonstrate cancer phenotypes not observed in mouse KOs. In some cases, the cancers that arise in the KO hamster are similar to cancers that arise in humans, in contrast with KO mice that do not develop the cancers. An example is the development of aggressive acute myelogenous leukemia (AML) in TP53 KO hamsters. The review also presents a discussion of the relative strengths and weaknesses of mouse cancer models and hamster cancer models and argues that there are no perfect rodent models of cancer and that the genetically engineered hamster cancer models can complement mouse models and expand the suite of animal cancer models available for the development of new cancer therapies.

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Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers

Cited by 7 publications

References 158 publications

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Targeted therapy for head and neck cancer: signaling pathways and clinical studies

Patient-derived tumor models: a suitable tool for preclinical studies on esophageal cancer

Golden Syrian Hamster Models for Cancer Research

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