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Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity

Cancer Drug resistance 2023年第4期6卷 709-728页

作者： Hannah Zaryouh Ines De Pauw Hasan Baysal Joran Melis Valentin Van den Bossche Christophe Hermans Ho Wa Lau Hide Lambrechts Celine Merlin Cyril Corbet Marc Peeters Jan Baptist Vermorken Jorrit De Waele Filip Lardon An Wouters Center for Oncological Research(CORE) Integrated Personalized&Precision Oncology Network(IPPON)University of AntwerpCampus Drie EikenAntwerp 2610Belgium Pole of Pharmacology and Therapeutics(FATH) Institut de Recherche Experimentale et Clinique(IREC)UCLouvainBrussels B-1200Belgium institut Roi Albert Il Department of Medical OncologyCliniques Universitaires Saint-LucBrussels B-1200Belgium Department of Medical Oncology Antwerp University HospitalEdegem 2650Belgium

Aim:Acquired resistance to the targeted agent cetuximab poses a significant challenge in finding effective anti-cancer treatments for head and neck squamous cell carcinoma(HNSCC).To accurately study novel combination treatments,suitable preclinical mouse models for cetuximab resistance are key yet currently *** study aimed to optimize an acquired cetuximab-resistant mouse model,with preservation of the innate immunity,ensuring intact antibody-dependent cellular cytotoxicity(ADCC)***:cetuximab-sensitive and acquired-resistant HNSCC cell lines,generated in vitro,were subcutaneously engrafted in Rag2 knock-out(KO),BALB/c Nude and CB17 Scid mice with/without Matrigel or *** tumor growth was established,mice were intraperitoneally injected twice a week with cetuximab for a maximum of 3 *** addition,immunohistochemistry was used to evaluate the tumor and its ***:Despite several adjustments in cell number,cell lines and the addition of Matrigel,Rag2 KO and BALB/C Nude mice proved to be unsuitable for xenografting our HNSCC cell *** tumor growth of resistant SC263-R cells could be induced in CB17 Scid ***,these cells had lost their resistance phenotype in *** revealed a high infiltration of macrophages in cetuximab-treated SC263-R ***-S and FaDu-R cells successfully engrafted into CB17 Scid mice and maintained their sensitivity/resistance to ***:We have established in vivo HNSCC mouse models with intact ADCC functionality for cetuximab resistance and sensitivity using the FaDu-R and FaDu-S cell lines,*** models serve as valuable tools for investigating cetuximab resistance mechanisms and exploring novel drug combination strategies.

关键词： HNSCC cetuximab resistance xenograft mouse model immunodeficient mice

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