A perspective on patient-derived orthotopic xenograft (PDOX) mouse models for identification of novel and individualized treatment for sarcoma.

IF 2.8 3区医学 Q3 ONCOLOGY

International Journal of Clinical Oncology Pub Date : 2025-09-01 Epub Date: 2025-06-10 DOI:10.1007/s10147-025-02801-6

Takashi Higuchi, Kentaro Igarashi, Shinji Miwa, Hiroaki Kimura, Katsuhiro Hayashi, Satoru Demura, Sei Morinaga, Yohei Asano, Norio Yamamoto, Francis J Hornicek, Hiroyuki Tsuchiya, Robert M Hoffman

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引用次数: 0

Abstract

Sarcomas, including osteosarcoma and soft tissue sarcoma, are heterogeneous and rare diseases with limited treatment options and a high metastatic potential. Despite advancements in immunotherapy and targeted therapies, many sarcoma patients have limited durable responses to these treatments. Therefore, individualized precision medicine and novel drug discovery are greatly needed. To address this unmet need, we have developed a patient-derived orthotopic xenograft (PDOX) mouse model of sarcomas using surgical orthotopic implantation. The PDOX models more accurately recapitulate the complex characteristics of human tumors compared to traditional subcutaneous xenografts. This enhanced fidelity is due to the preservation of the original tumor's histology and the accurate representation of the tumor microenvironment within the orthotopic implantation site. The present report summarizes our research group's experience with the sarcoma PDOX model and underscores its significant potential for identifying effective therapeutics. We have obtained numerous promising and unexpected results, including the identification of active chemotherapy drugs, novel drug combinations, and experimental therapeutics tailored to individual patients. In the current era of growing advancements in precision medicine, PDOX models offer a unique opportunity for developing individualized and innovative therapy specifically tailored to the individual needs of sarcoma patients.

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基于患者源性原位异种移植（PDOX）小鼠模型的肉瘤新个体化治疗研究

肉瘤，包括骨肉瘤和软组织肉瘤，是一种异质性和罕见的疾病，治疗选择有限，具有高转移潜力。尽管免疫治疗和靶向治疗取得了进展，但许多肉瘤患者对这些治疗的持久反应有限。因此，个性化的精准医疗和新药的发现是非常必要的。为了解决这一未满足的需求，我们开发了一种采用手术原位植入的患者源性原位异种移植（PDOX）肉瘤小鼠模型。与传统的皮下异种移植相比，PDOX模型更准确地概括了人类肿瘤的复杂特征。这种增强的保真度是由于保留了原始肿瘤的组织学和原位植入部位内肿瘤微环境的准确表示。本报告总结了我们研究小组在肉瘤PDOX模型方面的经验，并强调了其在确定有效治疗方法方面的重要潜力。我们已经获得了许多有希望的和意想不到的结果，包括活性化疗药物的鉴定，新的药物组合，以及针对个体患者的实验性治疗。在当前精准医疗不断进步的时代，PDOX模型为开发针对肉瘤患者个性化需求的个性化创新疗法提供了独特的机会。

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来源期刊

International Journal of Clinical Oncology 医学-肿瘤学

CiteScore

6.80

自引率

3.00%

发文量

175

审稿时长

2 months

期刊介绍： The International Journal of Clinical Oncology (IJCO) welcomes original research papers on all aspects of clinical oncology that report the results of novel and timely investigations. Reports on clinical trials are encouraged. Experimental studies will also be accepted if they have obvious relevance to clinical oncology. Membership in the Japan Society of Clinical Oncology is not a prerequisite for submission to the journal. Papers are received on the understanding that: their contents have not been published in whole or in part elsewhere; that they are subject to peer review by at least two referees and the Editors, and to editorial revision of the language and contents; and that the Editors are responsible for their acceptance, rejection, and order of publication.