Abstract 222: Establishment of patient-derived tumor organoids from head and neck cancers for predicting response to treatments

Abstract

Abstract The risk of relapse or recurrence of Head and Neck Squamous Cell Carcinoma (HNSCC) is high despite the combination of surgery and radiochemotherapy, responsible for high toxicity. It is crucial to develop new therapeutic strategies and to identify patients likely to benefit from these treatments. Patient-Derived Tumor Organoids (PDTO) are three-dimensional multicellular structures derived from patient tumor samples and faithfully reproduce the histological and molecular characteristics of the original tumor. A growing body of research indicates that PDTO may predict the clinical response, representing a major opportunity for the development of new therapeutic strategies and precision medicine. The purpose of this translational study is to generate PDTO from HNSCC patients to evaluate their predictive value. PDTO were obtained after dissociation of tumor specimen of HNSCC patients through the setup of the clinical study ORGAVADS (NCT04261192). Tumor cells were embedded in extracellular matrix and cultured in specific medium. Histological and immunohistochemical characterizations were performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovative therapies were evaluated by live-cell imaging and viability assays. The culture conditions were optimized to improve the success rate of PDTO establishment which now exceeded 50%. Twenty-one PDTO lines have been established and showed histological characteristics close to the original tumor. Expression of immunohistochemical tumor markers p53, p40, p63, and p16 were similar in tumors and paired PDTO. Functional assays were performed on 15 PDTO to analyze the response to treatments (cisplatin, olaparib, X-Rays) and heterogeneity of response was observed between the models. When clinical response was available, PDTO derived from good responders showed high sensitivity to treatments while PDTO from bad responders showed low sensitivity to treatments. Interestingly, two PDTO lines derived from HPV+ oropharyngeal tumors displayed very high sensitivity to cisplatin, matching with the patient's profile and response. Our results showed feasibility to derive PDTO from HNSCC and to perform functional assay to assess their response to different treatments. The first studies of correlation between PDTO and patient responses are promising and will be further investigated in more patients. This will allow to demonstrate the predictive value of PDTO from HNSCC with the purpose to develop a clinically compatible predictive functional assay. Citation Format: Marion Perréard, Vianney Bastit, Lucie Lecouflet, Guillaume Desmartin, Romane Florent, Corinne Jeanne, Juliette Thariat, Emmanuel Babin, Laurent Poulain, Louis-Bastien Weiswald. Establishment of patient-derived tumor organoids from head and neck cancers for predicting response to treatments [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 222.