Abstract 224: Combining functional precision medicine and radiotherapy with bio-printed organoids in head and neck squamous cell carcinoma

Abstract The study aims to establish a high throughput ex vivo organoid-based drug screening platform for head and neck squamous cell carcinoma (HNSCC) to investigate interactions between radiotherapy and different chemotherapies or targeted therapy agents and ultimately provide functional precision medicine therapeutic suggestions. HNSCC is the sixth most common cancer worldwide. Both HPV+ and HPV- cancers can be treated with surgery, radiotherapy, chemotherapy, or a combination of these. Cetuximab is currently the only FDA-approved targeted agent for HNSCC. Few clinical trials to date have shown an improved clinical outcome when combining targeted agents with radiotherapy, thus there is a need to identify new therapeutic combinations to improve outcomes. In order to characterize HNSCC tumor behavior and sensitivity to therapy, we have leveraged our high throughput 3D tumor organoid screening platform. Our approach entails seeding tumor cells in extracellular matrix around the perimeter of tissue culture wells in ring-like structures, which we have successfully deployed in other cancer types (Phan et al, 2019; Al Shihabi et al, 2022; Nguyen et al, 2022; Al Shihabi et al 2023). To optimize a chemoradiation platform, we used the HN30, HN31, and SCC154 cell lines representing HPV- primary, HPV- metastatic, and HPV+ head and neck tumors. The cell-line-derived 3D models are exposed to both radiotherapy and various chemotherapy or targeted therapy drugs. We measured cell responses by ATP-release assays and by applying our machine learning-based brightfield image analysis pipeline (Al Shihabi et al, 2022). Our results showed that the HPV+ SCC154 was the most sensitive line to radiotherapy while HPV- metastatic HN31 was the most resistant. HN31 was resistant to most drug treatments except for gemcitabine, docetaxel, and mitomycin c, while HN30 and SCC154 were sensitive to a broader set of agents. We have investigated combinatorial efficacy of radiation and chemotherapy as well as targeted agents and extended this platform to HNSCC patient-derived tumor organoids. Our proof-of-concept study highlights how our organoid-based drug screening platform can be used to test chemoradiation approaches that are more effective and personalized. Citation Format: Luda Lin, Krishna K. Bommakanti, Andreanne V. Sannajust, Yazeed Alhiyari, Brandon Mo, Lauran Evans, Peyton Tebon, Maie St. John, Alice Soragni. Combining functional precision medicine and radiotherapy with bio-printed organoids in head and neck squamous cell carcinoma 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 (6Suppl): Abstract nr 224.