Abstract B096: Response to approved anticancer drugs by multi-cell type tumor spheroids versus organoids derived from the same clinical specimen: a comparison analysis

Abstract Several types of 3D cell culture models are in use in cancer research to test drugs and investigational agents with a goal of bringing cell-based assays closer to the tumor. In 2013, the NCI began development of the Patient-Derived Models Repository as a resource of well-characterized matched xenografts (PDX), organoids (PDOrg), and cell lines (PDC) derived from the same patient samples (https://pdmr.cancer.gov). The PDMR currently maintains >1000 publicly available models. The current study, focused on colon and pancreatic carcinomas, compared responses of matched multi-cell type tumor (mct)-spheroids (composed of malignant cells with human endothelial cells and mesenchymal stem cells) and PDOrgs after a 7-day exposure to approved anticancer drugs. The mct-spheroids were maintained in liquid media in U-bottom ultra-low attachment plates and the organoids were maintained in media containing basement membrane extract. Responses were assessed over 2-logs of viability and 4-logs of drug concentration with a CellTiter-Glo 3D endpoint. Compared to the corresponding mct-spheroid, 4/12 (33%) colon carcinoma PDOrgs were more responsive to paclitaxel and 3/12 (25%) were less responsive. With 3D pancreatic carcinoma cultures, 3/8 (38%) PDOrgs were more responsive and 1/8 (13%) was less responsive than the corresponding mct-spheroids to paclitaxel. Paclitaxel achieved IC90 in 3 colon carcinoma mct-spheroids, 6 colon carcinoma PDOrgs, 1 pancreatic carcinoma mct-spheroid and 3 pancreatic carcinoma PDOrgs. In response to 5-FU, 3/12 (25%) colon carcinoma PDOrgs were more responsive than the mct-spheroids, while responses of the remaining models were comparable. For 5/8 (63%) pancreatic carcinoma models, responses of the PDOrgs and mct-spheroids to 5-FU were in agreement. Following 5-FU treatment, IC90 was reached in 0 colon carcinoma mct-spheroids, 7 colon carcinoma PDOrgs, 2 pancreatic carcinoma mct-spheroids, and 5 pancreatic carcinoma PDOrgs. Upon exposure to gemcitabine, 7/15 (47%) colon carcinoma PDOrgs were more responsive than the mct-spheroids, while only 1/15 (7%) was less responsive. Three of 8 (38%) pancreatic carcinoma PDOrgs were more responsive to gemcitabine than the corresponding mct-spheroids and 2/8 (25%) were less responsive. IC90 was achieved in 5 colon carcinoma mct-spheroids, 11 colon carcinoma PDOrgs, 5 pancreatic carcinoma mct-spheroids, and 6 pancreatic carcinoma PDOrgs following treatment with gemcitabine. Responses to erlotinib were similar in the PDOrgs and mct-spheroids in 8 models derived from pancreatic carcinoma, penile squamous carcinoma, colon carcinoma, Ewing sarcoma, uterine carcinosarcoma, NSCLC and a small intestine carcinoma. There was no consistent trend for PDOrgs to be more or less responsive than the corresponding mct-spheroids. This project was funded in whole or in part with funds from the National Cancer Institute, National Institutes of Health, under contract 75N91019D00024. Citation Format: Beverly A. Teicher, Nathan P. Coussens, Thomas S. Dexheimer, Thomas E. Silvers, Eric Jones, Dianne Newton, Luke Stockwin, James H. Doroshow. Response to approved anticancer drugs by multi-cell type tumor spheroids versus organoids derived from the same clinical specimen: a comparison analysis [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2025 Oct 22-26; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2025;24(10 Suppl):Abstract nr B096.