Application of PDX model in the evaluation of nano-delivery systems / 药学学报

Malignant tumor is a major disease affecting human health. The nano-delivery system itself has a unique size effect and it can achieve tumor-targeted distribution of drug molecules, improve the therapeutic effect, and reduce the toxic and side effects on normal tissues and cells after functional modification. Patient-derived xenografts (PDX) models can be established by transplanting patient-derived cancer cells or small tumor tissue into immunodeficient mice directly. Compared with the tumor cell line model, this model can preserve the key features of the primary tumor such as histomorphology, heterogeneity, and genetic abnormalities, and keep them stable between generations. PDX models are widely used in drug evaluation, target discovery and biomarker development, especially providing a reliable research platform for the diagnosis and treatment evaluation of nano-delivery systems. This review summarizes the application of several common cancer PDX models in the evaluation of nano-delivery systems, in order to provide references for researchers to perform related research.

Establishment of the patient derived liver cancer xenograft model / 中华肝胆外科杂志

Objective:To establish the patient derived xenograft (PDX) model of liver malignant tumor, analyze the related factors affecting the carcinogenesis of PDX model, and analyze the differences of biological characteristics between the primary tumor and PDX model.Methods:Fresh liver malignant tumor tissue samples were collected from the patients who received the surgery from the Tianjin First Central Hospital and the samples were inoculated subcutaneously into BALB/c-nu mice. The correlations between clinicopathological information and tumor formation rate were analyzed, and the pathological morphology and specific protein expression of PDX model and primary tumor were compared.Results:Thirty-three PDX models were successfully established from 63 cases of liver malignant tumors. The overall tumor formation rate was 52.4% (33/63), including 46.3% (25/54) of primary liver cancer and 88.9% (8/9) of liver metastasis. The main factors affecting the tumor formation rate were tumor pathological type, distant metastasis and TNM stage (all P<0.05). The pathological morphology and specific protein expression of PDX model and primary tumor were similar. Conclusion:The PDX model of liver malignant tumor was successfully constructed, and the tumor formation rate was high, and can maintain the biological characteristics of the primary tumor.

Expanding the concept of patient-derived xenografts cohorts in head and neck cancer: current and future perspectives / 华西口腔医学杂志

Head and neck cancer is the seventh common cancer in the world, and various existing treatment strategies provide modest benefit for most patients with head and neck cancer. Meanwhile, therapeutic strategies lacking molecular typing significantly hinder the development of individualized treatment for head and neck cancer. In recent years, connected by preclinical models, the novel ideal has gradually reached a consensus in terms of facilitating inter-transformation of clinical problems and basic achievements. As a bridge between basic research and clinical transformation, patient-derived xenografts (PDX) models precisely replicate genetic characteristics and tumor evolution, which are displaying great vitality in elucidating the mechanism of tumorigenesis and progression. Moreover, cohorts composed of several PDX models highlight the unique advantages of mice for drug screening and biomarker analysis for patients. This ideal preclinical model explores potential treatment strategies suited the ethical standards as much as possible for patients.

Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing. MATERIALS AND METHODS: To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA). RESULTS: Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25,HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845). CONCLUSION: We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

Generation and application of patient-derived xenograft models in pancreatic cancer research / 中华医学杂志(英文版)

Objective@#Pancreatic ductal adenocarcinoma cancer (PDAC) is one of the leading causes of cancer-related death worldwide. Hence, the development of effective anti-PDAC therapies is urgently required. Patient-derived xenograft (PDX) models are useful models for developing anti-cancer therapies and screening drugs for precision medicine. This review aimed to provide an updated summary of using PDX models in PDAC.@*Data sources@#The author retrieved information from the PubMed database up to June 2019 using various combinations of search terms, including PDAC, pancreatic carcinoma, pancreatic cancer, patient-derived xenografts or PDX, and patient-derived tumor xenografts or PDTX.@*Study selection@#Original articles and review articles relevant to the review’s theme were selected.@*Results@#PDX models are better than cell line-derived xenograft and other models. PDX models consistently demonstrate retained tumor morphology and genetic stability, are beneficial in cancer research, could enhance drug discovery and oncologic mechanism development of PDAC, allow an improved understanding of human cancer cell biology, and help guide personalized treatment.@*Conclusions@#In this review, we outline the status and application of PDX models in both basic and pre-clinical pancreatic cancer researches. PDX model is one of the most appropriate pre-clinical tools that can improve the prognosis of patients with pancreatic cancer in the future.

Establishment of metastatic colorectal cancer patient-derived xenografts models by image-guided biopsy / 中国癌症杂志

Background and purpose: Current colorectal cancer patient-derived xenografts (PDXs) models were established by samples taken during surgery. However, metastatic colorectal cancer (mCRC) patients have less surgical opportunities, and it was difcult to obtain enough tumor fragment. The aim of the present study was to es-tablish mCRC PDXs by image-guided biopsy. Methods: A total of 12 patients with colorectal cancer who underwent surgery were included. All patients had recurrent lesions or metastatic lesions needed to be histologically confirmed, and none of them had contraindication to biopsy. Tumor tissues not required for clinical diagnosis were used to establish mCRC PDXs. Results: Seven PDXs grew sufficiently for transfer into mice. The success rate was 77.8%. Conclusion:The PDXs established by image-guided biopsy had the advantage of convenient operation, good reproducibility, high achievement ratio, short experimental periodicity and reliably retain specific genetic and morphological features of the primary patient tumors.

Research progress of patient-derived xenografts in precision cancer medicine / 中国比较医学杂志

Cancer is a group of heterogeneous disease caused by diverse genomic alterations in oncogenes and tumor suppressor genes .Despite recent advances in high-throughput sequencing technologies and development of targeted therapies, novel cancer drug development is limited due to the high attrition rate from clinical studies .Patient-derived xenografts ( PDX) models are generated by implanting sectioned patient tumor fragments into immunodeficient mice .PDX models retain many of the key characteristics of patients ' tumors including histology , genomic signature , cellular heterogeneity , and drug responsiveness .These models cannot only serve as a platform for co-clinical trials by enabling the integration of clinical data , genomic profiles , and drug responsiveness data to determine precisely targeted therapies , but also be applied to the development of biomarkers for drug responsiveness and personalized drug selection .This review summarizes our current knowledge of this field , including methodologic aspects , applications in drug development , challenges and limitations , and utilization for precision cancer medicine .

Problems and strategies in the research of patient-derived gastric cancer xenograft models / 中国实验动物学报

In this paper, we summarize the major problems existing in establishing gastric cancer patient-derived xenograft ( PDX) models and its solutions, and introduce its advantages on screening targeted drugs. As many previous re?search emphasized on individual characteristics too much, we argue that we should pay more attention to the generality of what we are studying in order to analyze the genotype of PDX models before taking a targeted therapy.

New preclinical mouse model: Patient-derived xenografts / 肿瘤

The mouse models of nude mice bearing subcutaneous xenografts derived from tumor cell lines provide a preclinical testing system for exploring novel anticancer therapies. However, due to the lack of heterogeneity and an ability of spontaneous distant metastasis, these traditional models are difficult to accurately simulate the clinical condition of the patient. Recently, some researchers have developed better preclinical models by using patient-derived xenografts (PDXs) in mice. It has been shown that transplanting a variety of patient-derived tumor tissues into an appropriate anatomical site of immunocompromised or transgenic mice can authentically mimic the primary tumor in patients, especially with distant metastatic ability. PDXs can not only faithfully preserve the molecular phenotypes and genomic alterations of the primary tumors in patients, but also reproduce the heterogeneity of primary tumors; therefore, PDXs have been used in investigation of mechanism of drug resistance. This review summarizes the methodology of establishing PDXs, verification of similarity in original tumor and the corresponding xenograft, and the value and limitations of PDXs used in the development of new drugs. Copyright © 2014 by TUMOR.