Histologic and Molecular Analysis of Patient Derived Xenografts of High-Grade Serous Ovarian Carcinoma
Open accessAbstract
BACKGROUND: Patient derived xenografts (PDX) are generated by transplanting the original patient's tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. METHODS: In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. RESULTS: Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. CONCLUSION: Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC.
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Alterations in steroid hormone receptors and immune response genes have been reported in PDX models, irrespective of the maintained mutational profile.
“although alterations in steroid hormone receptors and immune response genes have been reported, irrespective of the maintained mutational profile (Dong et al., 2016).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Dong et al., 2016
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Yee, C., Dickson, K.-A., Muntasir, M. N., Ma, Y., & Marsh, D. J. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.836984 · Cited by 66 · see citing works
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- Authors
- Dong, R., Qiang, W., Guo, H., Xu, X., Kim, J. J., Mazar, A., Kong, B., & Wei, J.-J.
- Affiliations
- Northwestern University (US)
- Shandong University (CN)
- Corresponding author
- Kong, Beihua
- Wei, Jian-Jun
- ORCID
- Venue
- Journal of Hematology & Oncology
- Published
- 2016-09-21
- Volume
- 9
- Issue
- 1
- Pages
- 92-92
- ISSN
- 1756-8722 (ISSN-L)
- PMC
- PMC5031262
- OpenAlex
- W2522225554
- Cited by
- 49
- References
- 44
- Citations by year
- 2025: 5 · 2024: 7 · 2023: 4 · 2022: 10 · 2021: 1 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 5
- FWCI
- 7.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Hematology & Oncology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- NIH NCI (R21CA167038)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- patient-derived xenografts, high-grade serous ovarian cancer, fallopian tube cancer, tumor histology, cancer stem cells, steroid hormone receptors, tumor heterogeneity, personalized treatment, drug development
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