Organoid Models of Human and Mouse Ductal Pancreatic Cancer

By S. Boj, Chang-Il Hwang, Lindsey A. Baker, I. I. C. Chio, Dannielle D. Engle, V. Corbo, M. Jager, M. Ponz-Sarvisé, H. Tiriac, M. Spector and 38 more. Cell, 2014

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SUMMARY Pancreatic cancer is one of the most lethal malignancies due to its late diagnosis and limited response to treatment. Tractable methods to identify and interrogate pathways involved in pancreatic tumorigenesis are urgently needed. We established organoid models from normal and neoplastic murine and human pancreas tissues. Pancreatic organoids can be rapidly generated from resected tumors and biopsies, survive cryopreservation and exhibit ductal- and disease stage-specific characteristics. Orthotopically transplanted neoplastic organoids recapitulate the full spectrum of tumor development by forming early-grade neoplasms that progress to locally invasive and metastatic carcinomas. Due to their ability to be genetically manipulated, organoids are a platform to probe genetic cooperation. Comprehensive transcriptional and proteomic analyses of murine pancreatic organoids revealed genes and pathways altered during disease progression. The confirmation of many of these protein changes in human tissues demonstrates that organoids are a facile model system to discover characteristics of this deadly malignancy.

Subfields: Oncology, Surgery

View Paper: https://www.semanticscholar.org/paper/252abce25b1cb96dc23504b26e638c6039718ff1

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Citations in the corpus

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. (2019, background): “Organoids have since been applied to model various cancers, including pancreatic, prostate, liver, breast, bladder, ovarian, and gastrointestinal cancers (Boj et al., 2015; Broutier et al., 2017; Gao et al., 2014; Kopper et al., 2019; Lee et al., 2018; Sachs et al., 2018; Yan et al., 2018).”
Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. (2019, methodology): “Adjacentnormal specimens from human patients were minced and digested in Human Normal Organoid media (58) supplemented with Collagenase XI (Sigma C7657, 5 mg/mL), Y-27632 (STEMCELL Technologies, 10.”
IL-1-induced JAK/STAT signaling is antagonized by TGF-β to shape CAF heterogeneity in pancreatic ductal adenocarcinoma. (2018, methodology): “Orthotopic injections were conducted as previously described (17).”
Organoid profiling identifies common responders to chemotherapy in pancreatic cancer (2018, methodology): “Using advances in organoid culture technology, we 129 established the methodology to culture PDAC patient-derived organoids (PDOs) from both surgical 130 resection specimens as well as fine needle biopsies (FNB) with a high success rate (15, 16).”
Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I (2020, positive): “Mouse PDAC cells grown as organoids 25 exhibited considerable heterogeneity in autophagy flux, which closely resembled that of orthotopic tumours (Extended Data Fig.”
A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. (2018, neutral): “We and others have successfully generated organoids from primary colon, prostate, and pancreatic cancers (Boj et al., 2015; Fujii et al., 2016; Gao et al., 2014; Sato et al., 2011; van de Wetering et al., 2015) and explored the potential advantages of organoid cultures in allowing functional tests…”
Modeling Development and Disease with Organoids. (2016, background): “1594 Cell 165, June 16, 2016 more than one culture condition can be applied to efficiently grow human pancreas cancer organoids (Boj et al., 2015; Huang et al., 2015).”
Organoid modeling of the tumor immune microenvironment (2018, methodology): “Such PDOs allow human in vitro immunotherapy modeling via unified culture of tumor epithelium together with their native syngeneic, autologous tumor-reactive TILs, as opposed to epithelial-only organoid models (Boj et al., 2015; Fujii et al., 2016; Sato et al., 2011; van de Wetering et al., 2015), o”
High-Resolution CRISPR Screens Reveal Fitness Genes and Genotype-Specific Cancer Liabilities. (2015, neutral): “We observe multiple hits downstream of the driver mutations in all three MAPK pathway mutants (Figure 4B), including selective PI3K dependency in the KRAS mutant background, consistent with KRAS activation of the PI3K/AKT pathway (Boj et al., 2015; Castellano and Downward , 2011).”