Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling
Background: High-grade endometrial cancer (EC) has a poor prognosis, but molecular classification-based treatments present new therapeutic opportunities. Antibody-drug conjugates (ADC) emerge as promising tools, yet a deeper understanding of antigen dynamics, optimal therapeutic sequencing, and resi...
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Elsevier
2025-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558625000375 |
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| author | Sho Sato Shigehiro Yagishita Hiroshi Yoshida Daisuke Shintani Aiko Ogasawara Tadaaki Nishikawa Masanori Yasuda Keiji Furuuchi Toshimitsu Uenaka Akinobu Hamada Kosei Hasegawa |
| author_facet | Sho Sato Shigehiro Yagishita Hiroshi Yoshida Daisuke Shintani Aiko Ogasawara Tadaaki Nishikawa Masanori Yasuda Keiji Furuuchi Toshimitsu Uenaka Akinobu Hamada Kosei Hasegawa |
| author_sort | Sho Sato |
| collection | DOAJ |
| description | Background: High-grade endometrial cancer (EC) has a poor prognosis, but molecular classification-based treatments present new therapeutic opportunities. Antibody-drug conjugates (ADC) emerge as promising tools, yet a deeper understanding of antigen dynamics, optimal therapeutic sequencing, and resistance mechanisms is essential. This study investigates the utility of patient-derived xenograft (PDX) models for EC as preclinical platforms, evaluating molecular subtypes and the ADC targets expression of patient and PDX tumors. Methods: We developed a comprehensive panel of molecularly characterized PDX models from patients with EC representing various histological types. Molecular subtypes and gene alterations were analyzed using sequencing and immunohistochemistry. ADC targets, including human epidermal growth factor receptor 2, trophoblast cell-surface antigen 2, B7-H4, folate receptor alpha, and cadherin-6, were profiled. Results: Thirty-one EC-PDX models were successfully established, maintaining histological fidelity and 93.1 % molecular subtype consistency with the patient tumors. Notably, 80.6 % of the PDX models exhibited high expression (2+/3+) of at least one ADC target, and 54.8 % displayed high expression of multiple targets. Remarkably, 9.7 % showed high expression of all targets, with gene mutations also characterized. Meanwhile, patient tumors, 78.8 % showed high expression (2+/3+) of at least one ADC target, and 63.6 % showed high expression of multiple targets. Conclusion: The molecularly classified EC-PDX panel, enriched with detailed antigen profiles and genetic data, provides a robust platform for investigating novel ADC therapies and precision treatment strategies for high-grade EC. |
| format | Article |
| id | doaj-art-bcbf9a75f6ac4ef7bcb5ac7faf636689 |
| institution | DOAJ |
| issn | 1476-5586 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj-art-bcbf9a75f6ac4ef7bcb5ac7faf6366892025-08-20T03:13:22ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862025-06-016410115810.1016/j.neo.2025.101158Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profilingSho Sato0Shigehiro Yagishita1Hiroshi Yoshida2Daisuke Shintani3Aiko Ogasawara4Tadaaki Nishikawa5Masanori Yasuda6Keiji Furuuchi7Toshimitsu Uenaka8Akinobu Hamada9Kosei Hasegawa10Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, JapanDivision of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan; Department of Pharmacology and Therapeutics, National Cancer Center Research Institute, Tokyo, JapanDepartment of Diagnostic Pathology, National Cancer Center Hospital, Tokyo, JapanDepartment of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, JapanDepartment of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, JapanDepartment of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan; Department of Medical Oncology, National Cancer Center Hospital, Tokyo, JapanDepartment of Pathology, Saitama Medical University International Medical Center, Saitama, JapanEpochal Precision Anti-Cancer Therapeutics, Eisai Inc., Exton, PA, USAEpochal Precision Anti-Cancer Therapeutics, Eisai Inc., Exton, PA, USADivision of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan; Department of Pharmacology and Therapeutics, National Cancer Center Research Institute, Tokyo, Japan; Correspondence author at. Division of Molecular Pharmacology, National Cancer Center Research Institute, 5-1-1, Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.Department of Gynecologic Oncology, Saitama Medical University International Medical Center, Saitama, Japan; Correspondence author at. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan.Background: High-grade endometrial cancer (EC) has a poor prognosis, but molecular classification-based treatments present new therapeutic opportunities. Antibody-drug conjugates (ADC) emerge as promising tools, yet a deeper understanding of antigen dynamics, optimal therapeutic sequencing, and resistance mechanisms is essential. This study investigates the utility of patient-derived xenograft (PDX) models for EC as preclinical platforms, evaluating molecular subtypes and the ADC targets expression of patient and PDX tumors. Methods: We developed a comprehensive panel of molecularly characterized PDX models from patients with EC representing various histological types. Molecular subtypes and gene alterations were analyzed using sequencing and immunohistochemistry. ADC targets, including human epidermal growth factor receptor 2, trophoblast cell-surface antigen 2, B7-H4, folate receptor alpha, and cadherin-6, were profiled. Results: Thirty-one EC-PDX models were successfully established, maintaining histological fidelity and 93.1 % molecular subtype consistency with the patient tumors. Notably, 80.6 % of the PDX models exhibited high expression (2+/3+) of at least one ADC target, and 54.8 % displayed high expression of multiple targets. Remarkably, 9.7 % showed high expression of all targets, with gene mutations also characterized. Meanwhile, patient tumors, 78.8 % showed high expression (2+/3+) of at least one ADC target, and 63.6 % showed high expression of multiple targets. Conclusion: The molecularly classified EC-PDX panel, enriched with detailed antigen profiles and genetic data, provides a robust platform for investigating novel ADC therapies and precision treatment strategies for high-grade EC.http://www.sciencedirect.com/science/article/pii/S1476558625000375Endometrial cancerpatient-derived xenograft (PDX)antibody-drug conjugate (ADC) |
| spellingShingle | Sho Sato Shigehiro Yagishita Hiroshi Yoshida Daisuke Shintani Aiko Ogasawara Tadaaki Nishikawa Masanori Yasuda Keiji Furuuchi Toshimitsu Uenaka Akinobu Hamada Kosei Hasegawa Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling Neoplasia: An International Journal for Oncology Research Endometrial cancer patient-derived xenograft (PDX) antibody-drug conjugate (ADC) |
| title | Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling |
| title_full | Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling |
| title_fullStr | Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling |
| title_full_unstemmed | Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling |
| title_short | Establishing a comprehensive panel of patient-derived xenograft models for high-grade endometrial carcinoma: molecular subtypes, genetic alterations, and therapeutic target profiling |
| title_sort | establishing a comprehensive panel of patient derived xenograft models for high grade endometrial carcinoma molecular subtypes genetic alterations and therapeutic target profiling |
| topic | Endometrial cancer patient-derived xenograft (PDX) antibody-drug conjugate (ADC) |
| url | http://www.sciencedirect.com/science/article/pii/S1476558625000375 |
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