Abstract 6901: Paired colorectal and pancreatic cancer patient-derived tumor and organoids biobank

Abstract

Abstract Patient-derived xenograft (PDX) models constitute a crucial tool in precision cancer medicine owing to their high accuracy in predicting the response to therapeutic drugs among patients in clinical settings. Our center has established a biobank that collects more than 80 colorectal cancer and 25 pancreatic cancer PDX tissues, along with essential information about patients’ tumors and PDX models. However, cost-intensive and time-consuming limit the usage of PDX model in high throughput screening during drug development. To overcome this hurdle, we are generating a PDX-match paired organoid (PDXO) biobank by using emerging three-dimensional culture techniques. Before large-scaled expansion, the concordance between PDX tissues and PDXOs of partial specimens was evaluated firstly using short-tandem repeat (STR) analysis, immunohistochemistry (IHC) and H&E staining. Data of STR analysis performed by using AmpFLSTR Identifiler PLUS PCR Amplification Kit demonstrated that PDX tissues and PDXOs have identical DNA fingerprinting. IHC and H&E staining revealed PDX tissues and PDXOs have highly similar organ-specific markers expression (e.g., Cytokeratin 20, Caudal Type Homeobox 2, and Pan Cytokeratin) and histological morphology. Even after passing to at least five generations, passed PDXOs maintained high fidelity to their original state, as confirmed by whole-exome sequencing (WES) and STR analysis across passages. The WES analysis for passage 0 (P0) and passage 5 (P5) of PDXOs from different PDX tissues revealed there is more than 95% intersection between P0 and P5 PDXOs with the same missense mutation gene. The results of STR analysis showed that P0 and P5 PDXOs have identical STR profile. To evaluate the capability of PDXOs in clinical response prediction, several effective and ineffective drugs (e.g., oxapliplatin, 5-FU, gemcitabine) were tested. The results of drug testing indicated that PDXOs can be used to accurately predict the response to therapeutic drugs as PDX model but more efficient than PDX model. Therefore, PDXO biobank can serve as a valuable resource for high throughput in vitro drug screening prior in vivo efficacy confirmation using PDX models. Citation Format: Juiling Wang, Wen-Hui Ma, Yun-Chi Lo, Hsiao-Chun Hsieh, Li-Ju Hsiao, Yu-Pin Bau, Nai-Chieh Yang, Shaw-Jenq Tsai, Yan-Shen Shan, Tzu-Yu Chen, Yu-Ling Chen, Pei-Ju Chiang, Tzu-Ling Chen, Hsiu-Ping Chang, Hsian-Jean Chin. Paired colorectal and pancreatic cancer patient-derived tumor and organoids biobank [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(6_Suppl):Abstract nr 6901.