Development of preclinical models for the guidance of precision medicine. Development of preclinical models for the guidance of precision medicine. A,

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Development of preclinical models for the guidance of precision medicine. Development of preclinical models for the guidance of precision medicine. A, Of the 769 samples that have been run through the sequencing program, 50.9% were FFPE specimens, 44.5% were freshly collected tissue specimens, and a minority of 4.6% were from patients with hematologic malignancies sent to us as DNA specimens. B, 152/342 of the freshly collected specimens had a tissue biopsy or resection specimen to attempt the development of tumor organoids. Of these 152, 56 (36.8%) patient-derived organoids were successfully initiated from numerous tissues, including prostate (10/52), bladder/ureter (8/24), kidney (6/10), breast (4/6), colon/rectum (8/10), esophagus (1/6), soft tissue (3/6), brain (5/9), pancreas (5/7), lung (1/2), small intestine (2/3), ovary (1/1), and uterus (2/2). C, 22 of these patient-derived organoid models were subsequently injected into mice of which 19 organoid lines from colorectal cancer (CRC; n = 7), pancreatic ductal adenocarcinoma (PDAC; n = 3), uterine cancers (n = 2), neuroendocrine prostate cancer (NEPC; n = 2), renal cell carcinoma (RCC; n = 2), urothelial cancer (n = 1), lung adenocarcinoma (n = 1), and sarcoma (n = 1) successfully engrafted. D, Histology of primary tumor samples, tumor organoids, and xenografts from six different solid tumors: endometrial adenocarcinoma, pancreatic ductal adenocarcinoma, colorectal cancer, uterine carcinosarcoma, urothelial carcinoma, and renal cell carcinoma. Tumor organoid gross morphology (row 2) shows tumor type–specific structures such as the formation of lumina as seen for pancreas and colon. Tumor organoid and PDX histology shows conservation of the histopathologic features of the native tumors. Hematoxylin and eosin (H&E) stain from native tumor tissue, scale bar, 200 μm; tumor organoids bright field view in vitro, scale bar, 10 μm; H&E stain from tumor organoids, scale bar, 20 μm (urothelial carcinoma 200 μm); H&E stain from PDXs, scale bar, 20 μm. Chantal Pauli et al. Cancer Discov 2017;7:462-477 ©2017 by American Association for Cancer Research