Abstract 2404: Patient-derived organoid platform for the prediction of radiation response and modeling radiation resistance in oral cancer
Authors: Kang Sumin , Lee Mi Rim , Kong Sun-Young , Lee Jong-Ho , Kwon Dohyun , Kwon Ikjae , Kim Soung-Min , Kim Youngwook , Choi Wonyoung , Shon Hye Won , Lee Yu-Sun , Park Joo Yong , Choi Sung Weon , Kim Yun-Hee 
Published: April 2023

Abstract
Oral cancer is rare cancer that accounts for roughly 1.5% of all cancers in Korea. The standard treatment for the patient with oral cancer is surgery followed by radiotherapy. However, 30-50% of patients had local recurrence and metastasis to lymph nodes within 2 years. Numerous radiation-resistant cell lines have been created and utilized for research due to the significance of biomarkers for predicting response to radiation therapy; however, the homogenous 2D cell lines limit the practical use of the identified molecules. Patient-derived organoid (PDO) systems, as opposed to 2D cell lines, have significant advantages for the preclinical model in that they are similar to the genetic heterogeneity seen in patient tumors and reflect the clinical characteristics of patients. In this study, we generated organoid models that mimic radiation therapy from the oral PDO library in order to identify molecular profiles associated with radiation resistance. From January 2021 to August 2022, we prospectively collected 164 normal tissues and 179 tumor tissues from enrolled patients with oral cancer. 60 tumor organoids and 66 normal organoids were maintained over 4 passages and cryopreserved, which is the largest PDO repository with normal and malignant ever published for oral cancer to date. Each organoid was identified through long-term clinical information follow-up in their respective patients, notably recurrence after radiation therapy. In the oral PDO library, organoids were categorized as derived from tumor tissues of non-recurred patients (nPDOs), derived from primary tumor tissues of patients who recurred after radiotherapy (pPDOs), and derived from recurrent tumor tissues (rPDOs). There was also one pair of pPDO and rPDO for the same patient. A total of 60 Gy of radiation was irradiated to the organoids for the construction of a radiation-resistant PDO model, and finally, four cases of radiotherapy mimic organoid models were successfully established. Survival analysis for radiation dose-response and post-irradiation calcein-AM staining were used to validate these models. The pPDO and rPDO models of radiation resistance are well-established, whereas nPDO was not. Given the rarity of oral cancer, this platform is the first preclinical model to closely resemble the clinical radiation pipeline for patients with oral cancer. It would help make a more accurate prediction of radiation response in patients with oral cancer, as well as the development of treatment guidelines. (This research was supported by National Cancer Center, Korea (No. 2210980) and National Research Foundation of Korea (NRF) grant, funded by the Korean government (MSIT) (No. 2020M3A9A5036362))
Citation Format: Sumin Kang, Mi Rim Lee, Sun-Young Kong, Jong-Ho Lee, Dohyun Kwon, Ikjae Kwon, Soung-Min Kim, Youngwook Kim, Wonyoung Choi, Hye Won Shon, Yu-Sun Lee, Joo Yong Park, Sung Weon Choi, Yun-Hee Kim. Patient-derived organoid platform for the prediction of radiation response and modeling radiation resistance in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2404.