P24 | DEVELOPMENT OF HEAD AND NECK SQUAMOUS CELL CARCINOMA PATIENT-DERIVED XENOGRAFTS (PDXS) AND ORGANOIDS (PDXOS) FOR MORPHOLOGICAL ANALYSIS AND DRUG SCREENING

A. Francia¹, C. Girone¹, D.M. Filippini², G. Querzoli³, M. Fermi⁴, S. Venturoli⁵, A. Degiovanni⁶, C. Miroglio¹, E. Montacci¹, A. Ardizzoni⁷, M. Lauriola⁸, D. Romaniello⁸ | ¹Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; ²Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Division of Medical Oncology, IRCCS; Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ³Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Pathology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁴Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Department of Otorhinolaryngology-Head and Neck Surgery, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁵Microbiology Unit, IRCCS Azienda Ospedaliero-Universitaria of Bologna, Bologna, Italy; ⁶Pathology Unit, IRCCS Azienda Ospedaliero Universitaria di Bologna,Bologna, Italy; ⁷Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; ⁸Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Head and neck squamous cell carcinoma (HNSCC), arising from the oral cavity, larynx, and pharynx, represents the most prevalent tumour of the head and neck region. The epidermal growth factor receptor (EGFR) is often mutated or overexpressed in HNSCC, representing a key therapeutic target. The anti-EGFR monoclonal antibody cetuximab (CTX) was approved as a radiation sensitiser for recurrent or metastatic HNSCCs, but patients often develop resistance¹. Overall, therapeutic options for HNSCC remain limited and reliable models to study the disease are still lacking. Our research aims to develop reliable 3D models to study HNSCC and to provide a therapeutic alternative for patients resistant to the currently approved anti-EGFR therapy^2–4. Here, we established a set of Patient-Derived Xenografts (PDXs) by collecting tumour samples during surgical procedures and implanting them into immunocompromised mice (NODCB17Prkdcscid IL2rgtm1/Bc gen). The PDXs were subsequently expanded for drug testing and molecular analysis. Moreover, some of the tumours were processed to generate PDX Organoids (PDXOs) for further in vitro experiments. PDXOs were propagated in vitro in Matrigel, and the architecture ranged from solid dense spheres to hollow structures with a lumen, resembling glandular or cyst-like architecture. Most importantly, immunohistochemical characterisation of the PDXs and PDXOs confirmed the preservation of the patient-specific morphological and functional traits. In addition, immunohistochemical and molecular analysis revealed that EGFR expression varied across the samples, suggesting a heterogeneous response to EGFR inhibition. These results confirmed that PDXs and PDXOs represent a robust model to study HNSCC and constitute a fundamental step towards developing more effective and personalised therapeutic strategies.