Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity

Campbell, Katie M.; Lin, Tianxiang; Zolkind, Paul; Barnell, Erica K.; Skidmore, Zachary L.; Winkler, Ashley E.; Law, Jonathan H.; Mardis, Elaine R.; Wartman, Lukas D.; Adkins, Douglas R.; Chernock, Rebecca D.; Griffith, Malachi; Uppaluri, Ravindra

doi:10.1016/j.celrep.2018.07.058

Cited by 29 publications

(34 citation statements)

References 33 publications

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“…The development of xenograft mouse models has enabled the study of human tumor tissues and cell lines in vivo in immunodeficient mice. In light of the advantages as mentioned (127,128), and comparisons with other models or primary tumors (132,150). Nevertheless, xenograft mouse models are incapable of simulating the tumor microenvironment and cannot be used to study the interaction between tumors and host immunity because of the use of immunodeficient mice.…”

Section: Usage Of Xenograft Oscc Mouse Modelsmentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

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Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC.

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Section: Usage Of Xenograft Oscc Mouse Modelsmentioning

confidence: 99%

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Dong

Yang

et al. 2020

Front. Oncol.

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“…Animal models and organoids derived from patient tumors are two representative systems frequently adopted in cancer drug development. Patient-derived xenograft (PDX) mouse models where the patient's tumor tissue is transplanted into immunodeficient mice have demonstrated their usefulness to recapitulate patient's response to cancer agents in various types of cancers including breast, brain, colon, and lung tumors [6][7][8][9][10]. The banks of these ' Avatar' mice are valuable resources for preclinical tests.…”

Section: Introductionmentioning

confidence: 99%

Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data

et al. 2020

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Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

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“…Patient-derived xenograft (PDX) models have drawn increasing attention in preclinical oncology research owing to their ability to accurately recapitulate human tumor biology, including histopathologic, genetic and epigenetic features of tumors. [15][16][17] Further, the responses of PDXs to anti-cancer therapeutics have been found to closely correlate with response rates seen in patients. 18 As a result, Phase II type clinical trials of PDX models (PDX clinical trials) have been recently introduced as an experimental approach to interrogate interpatient response heterogeneity.…”

Section: Introductionmentioning

confidence: 98%

“…Patient‐derived xenograft (PDX) models have drawn increasing attention in preclinical oncology research owing to their ability to accurately recapitulate human tumor biology, including histopathologic, genetic and epigenetic features of tumors . Further, the responses of PDXs to anti‐cancer therapeutics have been found to closely correlate with response rates seen in patients .…”

Section: Introductionmentioning

confidence: 99%

A controlled trial of HNSCC patient‐derived xenografts reveals broad efficacy of PI3Kα inhibition in controlling tumor growth

Ruicci

Meens

Sun

et al. 2018

Intl Journal of Cancer

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Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K/AKT/mTOR signaling axis, particularly in the PIK3CA gene. PI3K‐targeted agents have therefore gained considerable preclinical and clinical interest as emerging therapies for HNSCC. Identification of predictive biomarkers of response would advance the clinical application of PI3K‐targeted drugs for patients, in order to achieve maximal benefit. To date, studies of drug biomarkers have largely focused on screening cell lines, with much more limited in vivo testing, usually only as validation. This approach has rarely enabled accurate predictions of clinical efficacy. Recently, clinical trials of PDX models (PDX clinical trials) have been introduced as a preclinical approach to interrogate interpatient response heterogeneity. Already, PDX clinical trial responses have been demonstrated to correlate closely with patient outcomes. Here, using both an HNSCC specific, 28‐cell line panel and a PDX clinical trial of 80 xenografts derived from 20 unique HNSCC tumors, we systematically examine patterns of response to PI3K inhibition in HNSCC. We find EGFR, AKT1 and CSMD1 copy number aberrations, but not PIK3CA mutations, to be associated with responsiveness to PI3K‐targeted drugs. Further, we reveal PI3Kα inhibition to be almost globally tumoristatic in HNSCC xenografts regardless of PIK3CA mutational status, emphasizing its potential as a stabilizing neoadjuvant therapy for HNSCC patients.

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Oral Cavity Squamous Cell Carcinoma Xenografts Retain Complex Genotypes and Intertumor Molecular Heterogeneity

Cited by 29 publications

References 33 publications

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Mouse Tumor-Bearing Models as Preclinical Study Platforms for Oral Squamous Cell Carcinoma

Validity of patient-derived xenograft mouse models for lung cancer based on exome sequencing data

A controlled trial of HNSCC patient‐derived xenografts reveals broad efficacy of PI3Kα inhibition in controlling tumor growth

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