Tumor tissue slice cultivation – high potential role in precision therapy of head and neck tumors (HNSCC)

Preclinical research rarely predict outcomes of clinical research. One main reason for translational failure is the incapacity of cell lines/animal models to reliably predict the complex and diverse tumor behavior in humans. This underlines the necessity of innovative tumor models. Tumor tissue slice cultivation is a patient-derived model preserving tumor cells and tumor microenvironment. Tumor biopsies were cut in 400 μm sections. The slices were cultivated on cell culture inserts at air-medium interface. Tumor-individual radiosensitivity-assays were performed and associated to clinical characteristics. We succeeded to cultivate over 50 HNSCC with the aim to understand specific radiobiology of HPV-positive oropharyngeal cancer (OPSCC): HPV-positive OPSCC tissues (n=14) showed a ATM-dependent defect in DNA damage repair (4.9 vs. 1.2 DNA double strand break foci per nucleus after 3 Gy; p <0.0001). The HPV-positive OPSCC samples derived from patients with smoking of 10 or more pack years (n=7) showed less intrinsic radiosensitivity than these without or little smoking exposure (p=0,0105). Analyse potential radiosensitizer: we tested dual targeting of PARP and the intra-S/G2 checkpoint through Wee1 inhibition for its radiosensitizing capacity. The combination appeared to be highly effective in HPV-negative locally advanced HNSCC (UICC: Stadium 4). Analyse radiosensitivity of rare tumors: intrinsic radiosensitivity of sinonasal squamous cell carcinoma is similiar to other HNSCC in the Hamburger tumor tissue slice cohort (n=6). Tumor tissue slices cultivation is an effective tool to examine individual radiosensitivity in HNSCC patients. In future, it could be used in clinical trials to stratify therapeutic responders from nonresponders and personalize treatment.