Tumor tissue slice cultivation – A translational tool to personalize (radio-)therapy in sinunasal squamous cell carcinoma (SNSCC)?

Introduction: Sinonasal squamous cell carcinoma (SNSCC) is a rare, heterogeneous, and difficult-to-treat cancer with limited understanding of its tumor biology. A multimodal treatment approach involving surgery and radio(chemo)therapy is often necessary, but tumor relapse is common. Patient-derived tumor tissue slices of SNSCC have the potential to personalize targeted (radio-)therapy for these patients. Therefore, we compare individual radiosensitivity and the radiosensitizing capacity of dual targeting PARP and the intra-S/G2 checkpoint through Wee1 inhibition in different specimens.Materials and Methods: Fresh patient-derived SNSCC samples were sectioned into 400 mm slices and cultured on cell culture inserts. The slice cultures were irradiated, either alone or in combination with PARP and Wee1 inhibition. After 2 and 24 hours, the samples were fixed and frozen. DNA double strand breaks (DSBs) were analyzed by quantifying 53BP1 foci in nuclei co-stained with the SCC marker p63 using immunofluorescence microscopy. Results: Tumor specimens from 7 patients were successfully cultivated ex vivo (success rate 88%). Immunofluorescence microscopy revealed areas of p63-positivity in all tumors. The number of residual DSBs varied significantly between SNSCC samples, indicating high heterogeneity between different tumors. However, intratumoral heterogeneity was low. Dual targeting with Wee1/PARP inhibition increased residual DSB levels in most tumors (4/6). Conclusion: Ex vivo cultivation of SNSCC is feasible and may predict individual radiosensitivity and response to targeted approaches, allowing for personalized therapeutic concepts for this rare cancer. In this context, combined inhibition of PARP and Wee1 shows promise as an approach that warrants further investigation.

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