DOI: 10.1002/ame2.70066
Establishment of a patient-derived drug-resistant oral squamous cell carcinoma animal model
Chuanni Feng1
Hao Liu2
Yalan Lu1
Yanfeng Xu1
Xinghan Wu1
Jinlong Wang1
Chuan Qin1
Binbin Li3
Yanhong Li1
1.NHC Key Laboratory of Human Disease Comparative Medicine,Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases,International Center for Technology and Innovation of Animal Model,Comparative Medicine Center,Institute of Laboratory Animal Sciences,Peking Union Medical College(PUMC),Chinese Academy of Medical Sciences(CAMS),Beijing,China2.The Central Laboratory,Peking University School and Hospital of Stomatology,Beijing,China3.Department of Oral Pathology,Peking University School and Hospital of Stomatology,Beijing,China
摘要：Oral squamous cell carcinoma(OSCC)constitutes 90％of oral tumors.Advanced cases severely impair patients' life quality of life due to anatomical location and limited ther-apies.Conventional treatments often induce drug resistance or recurrence.Patient-derived xenograft(PDX)models are widely used to simulate tumor progression and drug responses,serving as translational tools for precision medicine.This study aimed to establish drug-resistant OSCC PDX models.Human OSCC tissues were transplanted into immunodeficient mice and passaged(P1-P2).At P2(tumor volume:40-80mm3),mice received cisplatin(1 mg/kg,three times/week)with cetuximab(1 mg/kg,weekly),GSK690693(10mg/kg,five times/week),or rapamycin(4mg/kg,five times/week).PDX tissues from groups with less-therapeutic response(manifested as larger tumor volumes)were serially passaged to assess treatment efficacy.Tumor tissues with di-minished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin-eosin(HE)and immunohistochemi-cal staining after one additional passage and retreatment.Results demonstrated that successive passaging accelerates tumor growth.First-generation treatments showed universal sensitivity.At P2,cisplatin-cetuximab and rapamycin groups remained sen-sitive,whereas GSK690693 efficacy declined.Continued passaging of GSK690693-treated tumors confirmed resistance,as evidenced by exhibiting enhanced malignant characteristics at histological level.The GSK690693-resistant model was established first,whereas resistant models of other treatment groups were established according to similar protocols.These findings suggest that sequential passaging and drug expo-sure in PDX models recapitulated clinical tumor evolution,enabling the development of drug-resistant OSCC models.This study can offer methodological insights for pre-cision therapy of OSCC.
机标关键词：cellmodeloralanimalcarcinomadrug-resistantestablishmentpatient-derived
论文发表日期：2025-08-30
在线出版日期：2025-11-05（本平台首次上网日期，不代表文献的发表时间）
页数：11( 1513-1523 )
英文信息