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.