Establishment of a patient-derived drug-resistant oral squamous cell carcinoma animal model

Chuanni Feng; Hao Liu; Yalan Lu; Yanfeng Xu; Xinghan Wu; Jinlong Wang; Chuan Qin; Binbin Li; Yanhong Li

doi:10.1002/ame2.70066

Abstract：Oral squamous cell carcinoma (OSCC) constitutes 90% of oral tumors. Advanced cases severely impair patients' quality of life due to anatomical location and limited therapies. 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: 40-80 mm3), mice received cisplatin (1 mg/kg, three times/week) with cetuximab (1 mg/kg, weekly), GSK690693 (10 mg/kg, five times/week), or rapamycin (4 mg/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 diminished drug sensitivity underwent histopathological analysis and identified stability of their tumor characteristics using hematoxylin-eosin (HE) and immunohistochemical 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 sensitive, 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 exposure in PDX models recapitulated clinical tumor evolution, enabling the development of drug-resistant OSCC models. This study can offer methodological insights for precision therapy of OSCC.