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Establishment and preclinical application of a patient-derived xenograft model for uterine cancer

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Abstract
Background. The patient-derived xenograft (PDX) model is a promising translational platform for duplicating the characteristics of primary tumors. Here, we established and characterized PDX models of uterine cancer to demonstrate their utility for preclinical drug testing. Materials and methods. We generated PDX tumors surgically derived from 58 cases of uterine cancer. Subrenal capsule xenografts and primary tumors were compared using microscopic examination, short tandem repeat analyses, and targeted sequencing analyses. A phosphatidylinositol 3-kinase (PI3K) inhibitor was administered to mice whose PDX tumors harbored a PTEN deletion or PIK3CA mutation. We also generated an orthotopic PDX model using uterine horn implantation. Results. Thirty-three (56.9%) PDXs were successfully generated and passaged to maintain tumors. The histological features of the PDX tumors were stable over subsequent passages. By contrast, the proportions of epithelial and mesenchymal components of carcinosarcoma PDX models varied by generation. Targeted sequencing analyses revealed that all mutated cancer-related genes were stable during establishment and subgrafting. Treatment with a PI3K inhibitor cased a significant decrease in tumor weight in the clear cell carcinoma PDX harboring a frameshift PTEN deletion (p = 0.049) and in the serous carcinoma PDX harboring a missense PI3KCA mutation (p = 0.003) compared with matched controls. We also successfully established orthotopic PDX models (3/3; 100.0%). Conclusions. The histological and genetic features of PDXs were similar to those of primary tumors. This model is a promising translational platform for preclinical testing of new anticancer drugs and will enable the personalized development of therapeutic options for uterine cancer. (c) 2021 Elsevier Inc. All rights reserved.
Author(s)
정수영조영재류지윤최정주황재령김빛나리이유영김현수이정원
Issued Date
2021
Type
Article
Keyword
Orthotopic modelPatient-derived xenograftPhosphatidylinositol 3-kinase inhibitorSubrenal capsule implantationUterine cancer.
DOI
10.1016/j.ygyno.2021.04.028
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8298
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2525652577&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Establishment%20and%20preclinical%20application%20of%20a%20patient-derived%20xenograft%20model%20for%20uterine%20cancer&offset=0&pcAvailability=true
Publisher
GYNECOLOGIC ONCOLOGY
Location
미국
Language
영어
ISSN
0090-8258
Citation Volume
162
Citation Number
1
Citation Start Page
173
Citation End Page
181
Appears in Collections:
Medicine > Medicine
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