Abstract 6234: Development of a patient-derived organoid platform for predicting responses to standard treatments in oral cavity cancer

Abstract

Oral cancer is a rare cancer that occurs in the oral cavity, in areas such as the tongue, roof of mouth, floor of mouth, gum, and inside cheek. Oral cancer has frequent local recurrence and lymph node metastasis even after curative surgery with radiation to prevent recurrence. However, more than 50% of patients show a relapse pattern, and it is difficult to improve treatment due to the lack of experimental models that reflects the heterogeneity of the tumors as well as markers to predict treatment response. Although the patient-derived organoid (PDO) system is a good preclinical model that reflects the characteristics and heterogeneity of the original tumor, there are only small numbers of patients with oral cancer, so it has been relatively difficult to secure clinical samples. Therefore, oral cancer organoid development has so far been insufficient. Here, we have established a normal organoid library as well as cancer using primary tissue from many oral cancer patients. Seventy patients were enrolled in this study between Jan 2021 and Sep 2021. Fifty tumor organoids and fifty-five normal organoids were generated and sustained. Among them, 29 tumor organoids and 28 normal organoids were successfully cultured over 4 passages and cryopreserved. Moreover, 15 pairs of normal-tumor organoids were established. The success rate of organoids has no significant relationship with clinical information such as TNM stages, disease status and differentiation. These organoids recapitulated genomic features and histopathological characteristics of the patient tissue was examined through copy number variation (CNV) and IHC with TP53, P16, CK8, and so on, respectively. Normal organoids derived from tissue adjacent to the tumor of each patient showed typical morphology such as multilayer epithelium. Moreover, we set the assay system to evaluate the responses to radiation and the drug treatment using AUC value. Each organoid including normal and tumor showed different sensitivity to radiation. This oral cancer organoids platform is the largest repository in the field so far, apart from head and neck cancers. It provides a valuable platform for personalized treatment. It may also contribute to the discovery of factors associated with resistance or sensitivity to radiotherapy and chemotherapy in oral cavity cancer treatment. Citation Format: Sumin Kang, Mi Rim Lee, Sun-Young Kong, Jong-Ho Lee, Dohyun Kwon, Ikjae Kwon, Soung-Min Kim, Hye Won Shon, Yu-Sun Lee, Hyun-jin Kim, Joo Yong Park, Sung Weon Choi, Yun-Hee Kim. Development of a patient-derived organoid platform for predicting responses to standard treatments in oral cavity cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6234.