A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy

Zhang, Lianhai; Yang, Jie; Cai, Jie; Song, Xiaoming; Deng, Jianyun; Huang, Xuesong; Chen, Fan; Yang, Mengmeng; Wery, Jean-Pierre; Li, Shuangxi; Wu, Aiwen; Li, Ziyu; Li, Zhongwu; Liu, Yiqiang; Chen, Yiyou; Li, Qi-Xiang; Ji, Jiafu

doi:10.1038/srep02992

Cited by 80 publications

(83 citation statements)

References 21 publications

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“…For transcriptome sequencing of PDX tumor tissues, snap-frozen samples were used to extract RNAs per the method described previously (7,8). The purity and integrity of the RNA samples were ensured by Agilent Bioanalyzer prior to RNA-seq.…”

Section: Engraftment and Molecular Characterization Of Xenograft Tissuesmentioning

confidence: 99%

“…Methods and parameters regarding xenografting of patient tissues (Crown Bioscience SPF facility) have been described previously (7,8,10,11). For transcriptome sequencing of PDX tumor tissues, snap-frozen samples were used to extract RNAs per the method described previously (7,8).…”

Section: Engraftment and Molecular Characterization Of Xenograft Tissuesmentioning

confidence: 99%

“…Patient-derived xenografts (PDX) never manipulated in vitro are considered patient avatars and are used as an experimental model to study pathogenesis, to assess pharmaceutical effects, and to guide precision medicine (5)(6)(7)(8)(9). Various anecdotal reports have shown that the xenograft diseases mirror corresponding patient diseases in histopathology and molecular pathology.…”

Section: Introductionmentioning

confidence: 99%

“…If such similarity is systematically verified and further quantified, the translational utility of PDXs can be immensely explored and expanded. We have built a large library of PDXs over the years (7,8,(10)(11)(12)(13) and also performed transcriptome sequencing and/ or microarray analysis. The pathologic relevance of PDXs to patient tumors, both histologically and molecularly, can now be examined by comparing TCGA and PDX data.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines

Guo¹,

Qian²,

Cai³

et al. 2016

Cancer Research

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The Cancer Genome Atlas (TCGA) project has generated abundant genomic data for human cancers of various histopathology types and enabled exploring cancer molecular pathology per big data approach. We developed a new algorithm based on most differentially expressed genes (DEG) per pairwise comparisons to calculate correlation coefficients to be used to quantify similarity within and between cancer types. We systematically compared TCGA cancers, demonstrating high correlation within types and low correlation between types, thus establishing molecular specificity of cancer types and an alternative diagnostic method largely equivalent to histopathology. Different coefficients for different cancers in study may reveal that the degree of the within-type homogeneity varies by cancer types. We also performed the same calculation using the TCGA-derived DEGs on patient-derived xenografts (PDX) of different histopathology types corresponding to the TCGA types, as well as on cancer cell lines. We, for the first time, demonstrated highly similar patterns for within-and between-type correlation between PDXs and patient samples in a systematic study, confirming the high relevance of PDXs as surrogate experimental models for human diseases. In contrast, cancer cell lines have drastically reduced expression similarity to both PDXs and patient samples. The studies also revealed high similarity between some types, for example, LUSC and HNSCC, but low similarity between certain subtypes, for example, LUAD and LUSC. Our newly developed algorithm seems to be a practical diagnostic method to classify and reclassify a disease, either human or xenograft, with better accuracy than traditional histopathology. Cancer Res; 76(16); 4619-26. Ó2016 AACR.

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Section: Engraftment and Molecular Characterization Of Xenograft Tissuesmentioning

confidence: 99%

Section: Engraftment and Molecular Characterization Of Xenograft Tissuesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines

Guo¹,

Qian²,

Cai³

et al. 2016

Cancer Research

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“…PDTX models from various tumors have been established, such as colorectal cancer 17,18 , breast cancer 15,19 , nonsmall cell lung carcinoma 9,20 , and renal cell carcinoma 21 . PDTX models of gastric cancer using surgical tissues are reported occasionally [22][23][24] ; however, patients with AGC are the most suitable population to evaluate the efficacy of new drugs, and the major method to acquire tumor samples for AGC is gastroscopic biopsy, especially for paired samples before and after chemotherapy. …”

mentioning

confidence: 99%

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer.

Shen

Gao

Zhu

et al. 2015

JCO

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The patient-derived tumor xenograft (PDTX) model has become the most realistic model for preclinical studies. PDTX models of gastric cancer using surgical tissues are reported occasionally; however, the PDTX models using gastroscopic biopsies, which are best for evaluating new drugs, are unreported. In our study, a total of 185 fresh gastroscopic biopsies of gastric cancer were subcutaneously transplanted into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice. Sixty-three PDTX models were successfully established (34.1%, 63/185) and passaged to maintain tumors in vivo, and the mean latency period of xenografts was 65.86 6 32.84 days (11-160 days). Biopsies of prior chemotherapy had a higher transplantation rate (52.1%, 37/71) than biopsies after chemotherapy (21.9%, 25/114; P 5 0.000). No differences were found between the latency period of xenografts and characteristics of patients. The pathological and molecular features of PDTX as well as chemosensitivity were highly consistent with those of primary tumors of patients. The genetic characteristics were stable during passaging of PDTX models. In summary PDTX models using gastroscopic biopsies in gastric cancer were demonstrated for the first time, and the biological characteristics of the PDTX models were highly consistent with patients, which provided the best preclinical study platform for gastric cancer.T he percentage of advanced gastric cancer (AGC) in China is very high with poor prognosis and high mortality 1 . The comprehensive treatment based on fluorouracil containing chemotherapy is the main strategy for AGC. Although the addition of targeted drugs (trastuzumab, apatinib, and ramucirumab) [2][3][4] has improved the prognosis to some extent in recent years, the clinical outcome of AGC is not satisfactory due to the fewer therapeutic drugs and frequent drug resistance resulting from high heterogeneity and other mechanisms. As a consequence, developing new drugs and exploring the mechanisms of drug resistance are very urgent for AGC.Currently, the most commonly used models for developing new drugs are in vitro cell lines or in vivo animal models established by injection of cell lines 5,6 . With the rapid progression of scientific research, the above models are unable to meet the clinical needs. It is well known that almost all cell lines are subcultured many times in vitro and lose most features of patients 7,8 . Moreover, the microenvironment of in vitro cell lines is completely different from primary tumors of patients due to lack of tumor-associated stroma and blood supply, and so on 9 . A kind of ideal model is needed for the preclinical study.Patient-derived tumor xenograft (PDTX) models have become popular in the last several years with more advantages than cell line-based models [10][11][12] . Nowadays, most PDTX models are established by subcutaneously transplanting tumor tissues of patients into NOD/SCID (Nonobese Diabetic/Severe Combined Immunodeficiency) mice, and the biological characteristics of PDTX models are consistent w...

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Mouse Tumor Homografts Recapitulate Human Molecular Pathogenesis

Kumari¹,

Ouyang²,

Li³

2022

Animal Models for the Development of Cancer Immunotherapy

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A subset of gastric cancers with EGFR amplification and overexpression respond to cetuximab therapy

Cited by 80 publications

References 21 publications

Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines

Molecular Pathology of Patient Tumors, Patient-Derived Xenografts, and Cancer Cell Lines

Establishment and characterization of patient-derived tumor xenograft using gastroscopic biopsies in gastric cancer.

Mouse Tumor Homografts Recapitulate Human Molecular Pathogenesis

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