The Diverse Applications of Pancreatic Ductal Adenocarcinoma Organoids

Low, Ronnie Ren Jie; Lim, Wei‐Wen; Nguyen, Paul M.; Lee, Belinda; Christie, Michael; Burgess, Antony W.; Gibbs, Peter; Grimmond, Sean M.; Hollande, Frédéric; Putoczki, Tracy L.

doi:10.3390/cancers13194979

Cited by 12 publications

(10 citation statements)

References 180 publications

(364 reference statements)

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“…Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal malignancies, with a 5-year survival rate of less than 12% [ 1 ]. Many patients succumb to the disease within the first 6 months, reflecting late diagnosis, metastasis, and therapy resistance [ 2 , 3 ]. A distinctive feature of PDAC is the progression of early pancreatic intraepithelial neoplasia to an advanced unresectable disease [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

“…Many patients succumb to the disease within the first 6 months, reflecting late diagnosis, metastasis, and therapy resistance [ 2 , 3 ]. A distinctive feature of PDAC is the progression of early pancreatic intraepithelial neoplasia to an advanced unresectable disease [ 2 , 3 ]. During this process, the histopathological phenotype of the tumor changes from low-grade, characterized by well-formed glandular epithelial structures, to high-grade, whereby epithelial cells are diffuse throughout the desmoplastic stroma [ 2 , 3 ].…”

Section: Introductionmentioning

confidence: 99%

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S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

et al. 2023

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Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT, and mesenchymal states, each of which is associated with cancer progression, invasive capabilities, and ultimately, metastasis. We used a lineage-traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that underwent partial EMT and complete EMT. Using an unbiased proteomics approach, we found that organoid morphology predicts the EMT state, and the solid organoids are associated with a partial EMT signature. We also observed that exogenous TGFβ1 induces solid organoid morphology that is associated with changes in the S100 family, complete EMT, and the formation of high-grade tumors. S100A4 may be a useful biomarker for predicting EMT state, disease progression, and outcome in patients with pancreatic cancer.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

et al. 2023

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“…Pancreatic cancer represents one of the most lethal solid tumor types; pancreatic ductal adenocarcinoma accounts for 90% of these tumors, and less than 5% are pancreatic neuroendocrine neoplasms [96,97]. Pancreatic cancer organoids have been generated to investigate tumor biology and promote clinical applications [96,[98][99][100][101][102][103]. PDOs derived from primary pancreatic ductal adenocarcinoma (PDAC) and matched liver metastases were generated [104].…”

Section: Pancreatic Cancermentioning

confidence: 99%

“…Tumoroids also exert great potential in discovering novel tumor biomarkers [4,75,100]. Ukai S and colleagues developed and harvested 5-FU-resistant GCOs [75].…”

Section: Identification Of Novel Tumor Biomarkersmentioning

confidence: 99%

Tumor organoids: applications in cancer modeling and potentials in precision medicine

et al. 2022

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Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.

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“…A distinctive feature of PDAC is the progression of an early pancreatic intraepithelial neoplasia to advanced unresectable disease (Feldmann et al, 2007). During this process, the histopathological phenotype of a tumor changes from low grade, characterized by well-formed glandular epithelial structures, to high grade, whereby epithelial cells are diffuse throughout the desmoplastic stroma (Low et al, 2021; Schlitter et al, 2017). This process of dissemination has been linked to the activation of epithelial-mesenchymal transition (EMT), a cell-biological program that is essential to the early stages of embryogenesis, the formation of organs and exploited by cancer cells (Thiery, 2002; Yang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer

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Fung

Gao

et al. 2022

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Epithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased proteomics approach, we found that the morphology of the organoids predicts the EMT state, with solid organoids associated with a P-EMT signature. We also observed that exogenous TGF-beta1 induces a solid organoid morphology that is associated with changes in the S100 family, C-EMT and the formation of high-grade tumors. S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome for pancreatic cancer patients.

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The Diverse Applications of Pancreatic Ductal Adenocarcinoma Organoids

Cited by 12 publications

References 180 publications

S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

S100 family proteins are linked to organoid morphology and EMT in pancreatic cancer

Tumor organoids: applications in cancer modeling and potentials in precision medicine

TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer

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