Head and neck squamous cell carcinoma organoids as a platform for personalized medicine

Background: Organoids are 3D structures that recapitulate morphological, functional and genetic characteristics of the tissue of origin. Grown as organoids, primary cells can be kept in culture long-term without the requirement for immortalization or genetic alterations. In this study, we report the establishment of organoids derived of Head and Neck Squamous Cell Carcinomas (HNSCCs), which are tumors that arise from the squamous epithelium lining the oral cavity, pharynx and larynx. Overall five-year survival of patients diagnosed with this tumor is poor, and although many of the mutations detected in these tumors are therapeutically targetable, introduction of these treatment into the clinic has failed. Methods: Organoids are established from HNSCC biopsies or surgical resections. Subsequently, the organoids are characterized using histology and DNA and RNA sequencing. In vitro, organoids are tested for sensitivity to a range of drugs. Results: Here we report the establishment of organoids derived of HNSCCs. These structures seem to recapitulate genetic and histological features of the tumors of which they are derived. Upon drug exposure in vitro, these organoids show differential responses to different therapies, including cisplatin, carboplatin and the anti-EGFR antibody cetuximab, which are currently used in the clinic. Our data suggests that this system might have the potential to guide personalized therapy in the future. To validate these findings, we are currently setting up a study to test the predictive potential of patient-derived organoid lines for the first line treatment of HNSCC patients. We will expose tumor-derived organoids to these therapies. Retrospectively, organoid responses will be compared to patient response. The results of this study will show if, in this patient group, organoids can serve as a tool to guide therapy choice. Conclusions: This work suggests that HNSCC-derived organoids might have the potential to predict patient response, a hypothesis we will hope to validate by the study described above. Retrospectively, we will correlation patient outcome to in vitro organoid response. This will help us determine the potential of this system to predict therapy response of patients with HNSCC. Legal entity responsible for the study: Hans Clevers research group, Hubrecht Institute. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.