Stellate cells, a point of light in the dark night of pancreatic cancer

Ramírez, Natalia; Viúdez, A.; Hernández-García, Irene; Gourichon, David; Gómez-Dorronsoro, M.L.; Herrera, Fernández; Vila, Juan J.; Beloki, Lorea; Ciáurriz, Miriam; Mansilla, Cristina; Vera, Ruth

doi:10.1038/bjc.2014.59

Cited by 4 publications

(4 citation statements)

References 10 publications

(13 reference statements)

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“…They are related to be ‘partner in crimes' with pancreatic cancer cells (Vonlaufen et al , 2008) and to target them—especially in combination with other stroma-depleting or immune-modulatory agents—seems to be one of the most interesting therapeutic approaches of the last decade (Ramírez et al , 2014). In this context, an interim analysis of a phase II study investigating the combination therapy of gemcitabine, nab-paclitaxel and the hedgehog inhibitor vismodegib showed promising results (DeJesus-Acosta et al , 2014).…”

Section: Discussionmentioning

confidence: 99%

“…α -SMA is produced by activated pancreatic stellate cells and these fibroblast-like cells have multiple modulatory functions in the development of pancreatic cancer: activated by pancreatic cancer cells and activating these vice versa, they support the abundant stroma production present in most pancreatic cancers and promote tumour growth as well as invasiveness ( Erkan et al , 2012a , 2012b ). They are related to be ‘partner in crimes' with pancreatic cancer cells ( Vonlaufen et al , 2008 ) and to target them—especially in combination with other stroma-depleting or immune-modulatory agents—seems to be one of the most interesting therapeutic approaches of the last decade ( Ramírez et al , 2014 ). In this context, an interim analysis of a phase II study investigating the combination therapy of gemcitabine, nab-paclitaxel and the hedgehog inhibitor vismodegib showed promising results ( DeJesus-Acosta et al , 2014 ).…”

Section: Discussionmentioning

confidence: 99%

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α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study

et al. 2014

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Background:Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin (α-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of α-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients.Methods:CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of α-SMA expression and stromal density impact on patient outcome.Results:High α-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, α-SMA and stromal density expression were independently predictive factors for survival.Conclusions:Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

α-Smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study

et al. 2014

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“…PDAC is mainly characterized by its vascular deficiency and an abundant desmoplastic stroma, which usually represents 90% of tumor volume. The stroma is comprised of cancer-associated-fibroblasts, inflammatory cells, embedded in a rich and dense extracellular matrix [84,85,86]. Proteomic studies have been performed not only in fresh tissue, but also in preserved tissue such as formalin-fixed paraffin-embedded (FFPE) tissue.…”

Section: Proteomicsmentioning

confidence: 99%

Omics Approaches in Pancreatic Adenocarcinoma

González-Borja

Viúdez

Goñi

et al. 2019

Cancers

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Pancreatic ductal adenocarcinoma, which represents 80% of pancreatic cancers, is mainly diagnosed when treatment with curative intent is not possible. Consequently, the overall five-year survival rate is extremely dismal—around 5% to 7%. In addition, pancreatic cancer is expected to become the second leading cause of cancer-related death by 2030. Therefore, advances in screening, prevention and treatment are urgently needed. Fortunately, a wide range of approaches could help shed light in this area. Beyond the use of cytological or histological samples focusing in diagnosis, a plethora of new approaches are currently being used for a deeper characterization of pancreatic ductal adenocarcinoma, including genetic, epigenetic, and/or proteo-transcriptomic techniques. Accordingly, the development of new analytical technologies using body fluids (blood, bile, urine, etc.) to analyze tumor derived molecules has become a priority in pancreatic ductal adenocarcinoma due to the hard accessibility to tumor samples. These types of technologies will lead us to improve the outcome of pancreatic ductal adenocarcinoma patients.

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“…We read with great interest the comments made by Ramírez et al (2014) in which they highlight the importance of tumour stroma in pancreatic cancer (PDAC) and the role of ‘pancreatic stellate cells' in the development of tumour stroma. The current data, while with still some inconsistencies, show that in preclinical models of PDAC, the combination of gemcitabine and Nab-paclitaxel (PTX) increases the delivery of gemcitabine to the tumour.…”

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confidence: 99%