Understanding the Cellular Origin and Progression of Esophageal Cancer Using Esophageal Organoids

Patient-derived organoids (PDOs) from human tissue samples allow for unique and faithful in vitro modeling of esophageal cancers, and provide an exciting platform for investigation into personalized medicine and targeted treatment approaches
[Cancer Letters]
Sachdeva, U. M., Shimonosono, M., Flashner, S., Cruz-Acuña, R., Gabre, J. T., & Nakagawa, H. (2021). Understanding the cellular origin and progression of esophageal cancer using esophageal organoids. Cancer Letters. https://doi.org/10.1016/j.canlet.2021.03.031 Cite
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Modelling Hereditary Diffuse Gastric Cancer Initiation Using Transgenic Mouse-Derived Gastric Organoids and Single-Cell Sequencing

Using single‐cell RNA sequencing, researchers explored the transcriptional landscape of a murine organoid model of hereditary diffuse gastric cancer to characterize the impact of CDH1 loss in early tumorigenesis.
[Journal of Pathology]
Dixon, K., Brew, T., Farnell, D., Godwin, T. D., Cheung, S., Chow, C., Ta, M., Ho, G., Bui, M., Douglas, J. M., Campbell, K. R., El‐Naggar, A., Kaurah, P., Kalloger, S. E., Lim, H. J., Schaeffer, D. F., Cochrane, D., Guilford, P., & Huntsman, D. G. (n.d.). Modelling hereditary diffuse gastric cancer initiation using transgenic mouse-derived gastric organoids and single-cell sequencing. The Journal of Pathology, n/a(n/a). https://doi.org/https://doi.org/10.1002/path.5675 Cite
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Cannibalized Erythroblasts Accelerate Developmental Neurogenesis by Regulating Mitochondrial Dynamics

To investigate the role of junctional β-catenin in heme signaling, researchers employed neural organoids with stabilized intercellular junctions and an enhanced capacity for the recruitment of free cytoplasmic β-catenin.
[Cell Reports]
Özsoy, Ş., Vujovic, F., Simonian, M., Valova, V., Hunter, N., & Farahani, R. M. (2021). Cannibalized erythroblasts accelerate developmental neurogenesis by regulating mitochondrial dynamics. Cell Reports, 35(1). https://doi.org/10.1016/j.celrep.2021.108942 Cite
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Enhanced Anti-Cancer Activity of Andrographis with Oligomeric Proanthocyanidins through Activation of Metabolic and Ferroptosis Pathways in Colorectal Cancer

Scientists demonstrated the enhanced anti-cancer activity between two botanical extracts in terms of their ability to inhibit cancer cell growth, suppress colony formation and induce apoptosis. They validated these findings in subcutaneous xenograft models and in patient derived primary epithelial 3D organoids.
[Scientific Reports]
Shimura, T., Sharma, P., Sharma, G. G., Banwait, J. K., & Goel, A. (2021). Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer. Scientific Reports, 11(1), 7548. https://doi.org/10.1038/s41598-021-87283-y Cite
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Vangl2 Promotes the Formation of Long Cytonemes to Enable Distant Wnt/β-Catenin Signaling

Scientists showed that the planar cell polarity protein Vangl2 regulated the distribution of Wnt by cytonemes. They used an organoid formation assay to analyze the requirement for VANGL-dependent WNT cytonemes.
[Nature Communications]
Brunt, L., Greicius, G., Rogers, S., Evans, B. D., Virshup, D. M., Wedgwood, K. C. A., & Scholpp, S. (2021). Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nature Communications, 12(1), 2058. https://doi.org/10.1038/s41467-021-22393-9 Cite
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ADCK1 Activates the β-Catenin/TCF Signaling Pathway to Promote the Growth and Migration of Colon Cancer Cells

Researchers found an increase in ADCK1 (AarF domain-containing kinase 1) expression in clinical specimens of colon cancer and animal models. Downregulation of ADCK1 expression inhibited the colony formation and infiltration of cancer cells, in vivo tumorigenesis, migration, and organoid formation.
[Cell Death & Disease]
Ji, Y., Liu, Y., Sun, C., Yu, L., Wang, Z., Du, X., Yang, W., Zhang, C., Tao, C., Wang, J., Yang, X., Di, S., & Huang, Y. (2021). ADCK1 activates the β-catenin/TCF signaling pathway to promote the growth and migration of colon cancer cells. Cell Death & Disease, 12(4), 1–12. https://doi.org/10.1038/s41419-021-03624-9 Cite
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$2.5M award to fund joint organoid research program at Wake to treat aggressive cancers

Personalized medicine research for aggressive abdominal cancers at Wake Forest Baptist Health received a boost from a $2.5 million grant from the National Cancer Institute that supports research efforts at Wake Forest Organoid Research Center.
[Wake Forest Baptist Health (Newswise, Inc.)]
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Quantifying Single-Cell ERK Dynamics in Colorectal Cancer Organoids Reveals EGFR as an Amplifier of Oncogenic MAPK Pathway Signaling

To elucidate the interplay between epidermal growth factor signaling and extracellular-regulated kinase activation in tumors, scientists used patient-derived organoids from KRAS and BRAF mutant colorectal cancer.
[Nature Cell Biology]
Ponsioen, B., Post, J. B., Buissant des Amorie, J. R., Laskaris, D., van Ineveld, R. L., Kersten, S., Bertotti, A., Sassi, F., Sipieter, F., Cappe, B., Mertens, S., Verlaan-Klink, I., Boj, S. F., Vries, R. G. J., Rehmann, H., Vandenabeele, P., Riquet, F. B., Trusolino, L., Bos, J. L., & Snippert, H. J. G. (2021). Quantifying single-cell ERK dynamics in colorectal cancer organoids reveals EGFR as an amplifier of oncogenic MAPK pathway signalling. Nature Cell Biology, 1–14. https://doi.org/10.1038/s41556-021-00654-5 Cite
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FOXO3 Is a Latent Tumor Suppressor for FOXO3-Positive and Cytoplasmic-Type Gastric Cancer Cells

Treatment of FOXO3-Cyt human gastric cancer-derived organoids with an AKT inhibitor significantly suppressed the survival and proliferation.
[Oncogene]
Tsuji, T., Maeda, Y., Kita, K., Murakami, K., Saya, H., Takemura, H., Inaki, N., Oshima, M., & Oshima, H. (2021). FOXO3 is a latent tumor suppressor for FOXO3-positive and cytoplasmic-type gastric cancer cells. Oncogene, 1–15. https://doi.org/10.1038/s41388-021-01757-x Cite
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A Well Plate–Based Multiplexed Platform for Incorporation of Organoids into an Organ-on-a-Chip System with a Perfusable Vasculature

Investigators describe a detailed alternative method to cultivate millimeter-scale functional vascularized tissues on a biofabricated platform that enabled facile incorporation of organoid technology.
[Nature Protocols]
Lai, B. F. L., Lu, R. X. Z., Davenport Huyer, L., Kakinoki, S., Yazbeck, J., Wang, E. Y., Wu, Q., Zhang, B., & Radisic, M. (2021). A well plate–based multiplexed platform for incorporation of organoids into an organ-on-a-chip system with a perfusable vasculature. Nature Protocols, 1–32. https://doi.org/10.1038/s41596-020-00490-1 Cite
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Endothelial Wnts Control Mammary Epithelial Patterning via Fibroblast Signaling

To enable cell-type-specific gene manipulation in vitro, scientists establish an organoid system via coculture of endothelial cells (ECs), fibroblasts, and mammary epithelial cells.
[Cell Reports]
Wang, J., Song, W., Yang, R., Li, C., Wu, T., Dong, X. B., Zhou, B., Guo, X., Chen, J., Liu, Z., Yu, Q. C., Li, W., Fu, J., & Zeng, Y. A. (2021). Endothelial Wnts control mammary epithelial patterning via fibroblast signaling. Cell Reports, 34(13). https://doi.org/10.1016/j.celrep.2021.108897 Cite
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