Hua Yufei, Guo Zhiyong, Wang Ying, Li Chunjie, Yan Bing
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases & Research Unit of Oral Carcinogenesis and Management & Chinese Academy of Medical Sciences, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China.
Oral Oncol. 2025 Mar;162:107222. doi: 10.1016/j.oraloncology.2025.107222. Epub 2025 Feb 24.
The effect of radiotherapy and chemotherapy on head and neck chondrosarcoma (HNCS) has not been unanimously determined because of the rarity of HNCS. Patient-Derived Xenograft (PDX) model is considered to be a good preclinical model for new drug development and personalized drug screening. We performed this study to investigate the preclinical application and value of PDX model in drug screening for HNCS.
Tumor tissues of a patient with HNCS who underwent surgical treatment in the Department of Head and Neck Oncology of our hospital were collected. The PDX model was established in NCG mice and successfully passed to the P3 generation in nude mice. After the tumor grew to a certain size, three drugs targeting different molecules (Nilotinib, Regorafenib, Rapamycin) were given respectively. The treatment efficiency and safety were observed.
NCG mouse is a kind of mouse that can successfully establish the PDX model of HNCS, and the PDX model can be stably passed in nude mice. The PDX tumor show similar histopathological characteristics to the parent tumors. After stable passaging, the mesenchymal cells were reduced and the tumor cells were increased in PDX tumor, making it easier to extract primary tumor cells. In the P3 PDX tumor, oral administration of nilotinib and regorafenib or intraperitoneal injection of rapamycin could significantly reduce the tumor size.
For rare tumors such as HNCS, PDX model is a good preclinical model for personalized drug screening and has good clinical application value.
由于头颈部软骨肉瘤(HNCS)较为罕见,放疗和化疗对其的影响尚未得到一致定论。患者来源的异种移植(PDX)模型被认为是新药研发和个性化药物筛选的良好临床前模型。我们开展本研究以探讨PDX模型在HNCS药物筛选中的临床前应用及价值。
收集我院头颈肿瘤科一名接受手术治疗的HNCS患者的肿瘤组织。在NCG小鼠中建立PDX模型,并在裸鼠中成功传至P3代。待肿瘤长至一定大小时,分别给予三种靶向不同分子的药物(尼洛替尼、瑞戈非尼、雷帕霉素)。观察治疗效果及安全性。
NCG小鼠是一种能够成功建立HNCS的PDX模型的小鼠,且该PDX模型可在裸鼠中稳定传代。PDX肿瘤显示出与原发肿瘤相似的组织病理学特征。稳定传代后,PDX肿瘤中间质细胞减少,肿瘤细胞增多,使得更容易提取原代肿瘤细胞。在P3代PDX肿瘤中,口服尼洛替尼和瑞戈非尼或腹腔注射雷帕霉素可显著减小肿瘤大小。
对于HNCS等罕见肿瘤,PDX模型是个性化药物筛选的良好临床前模型,具有良好的临床应用价值。