269. PATIENT-DERIVED TUMOR ORGANOIDS AND XENOGRAFTS AS BASIC AND PRECLINICAL TRANSLATIONAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA MODELS

Abstract

Abstract Patient-derived xenografts have been gold standards for cancer modeling and drug testing. However, low establishment efficiency and high maintenance cost have hindered the development in the field. Recently, patient-derived tumor organoid (PDO) cultures have been developed as an efficient and economic model to mimic and recapitulate the original tumor tissue. Due to the limited availability of current esophageal squamous cell carcinoma (ESCC) models, we aimed to establish PDO cultures for ESCC study. We have established and biobanked a panel of ESCC PDO cultures in vitro from Chinese ESCC treatment-naïve patients undergoing an endoscopic examination or upfront surgery, or patients undergoing neoadjuvant chemoradiotherapy (CRT) followed by surgery in Hong Kong. We also established and maintained a panel of PDO-derived xenograft (PDOX) in immunocompromised mice. Genomic profiling showed consistent mutational landscapes of the established PDOs, as compared to ESCC patient profiles. Transcriptomic profiling suggests PDOs closely resemble patient tumor samples. In vitro chemotherapy treatments followed by prolonged recovery suggests the existence of a subpopulation of persistent cells likely enriched by neoadjuvant CRT and well-preserved by organoid cultivation. Coupled with live-cell bioluminescent-based quantification techniques, PDO cultures can be employed in high-throughput therapeutic screening. Immunohistochemical examination confirmed the squamous origin of the PDOs and PDOXs. Slow-proliferating PDOXs allow adequate interaction between the cancer cells and the host and are useful as a suitable preclinical drug testing platform. ESCC PDOs can be efficiently established from highly limited patient tissue samples and maintained long-term in vitro and can be feasibly integrated with mouse models. ESCC PDOs and PDOXs serve as novel models for ESCC basic and translational studies.