New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel

Laethem, Jean Luc Van; Verslype, Chris; Iovanna, Juan; Michl, Patrick; Conroy, Thierry; Louvet, Christophe; Hammel, Pascal; Mitry, Emmanuel; Ducreux, Michel; Maraculla, T.; Uhl, Waldemar; Tienhoven, Geertjan van; Bachet, Jean‐Baptiste; Maréchal, Raphaël; Hendlisz, Alain; Bali, Monia; Demetter, Pieter; Ulrich, Frank; Aust, D.; Lüttges, Jutta; Peeters, Marc; Mauer, Murielle; Roth, Arnaud; Neoptolemos, John P.; Lutz, Manfred P.

doi:10.1093/annonc/mdr351

Cited by 73 publications

(48 citation statements)

References 41 publications

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“…1 The median survival for those with metastatic disease is below 12 months even when treated with the most active chemotherapyregimens. 2,3 Radiotherapy appears to add little to the management of those with unresectable locally advanced disease.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Middleton

Silcocks

Cox

et al. 2014

The Lancet Oncology

312

197

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(2014) Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial. Lancet Oncology, 15 (8). pp. 829-840. ISSN 1474-5488 Access from the University of Nottingham repository: http://eprints.nottingham.ac.uk/43066/9/TeloVac%20Lancet%20Oncology%20Revised %208th%20May%202014.pdf Copyright and reuse:The Nottingham ePrints service makes this work by researchers of the University of Nottingham available open access under the following conditions. This article is made available under the University of Nottingham End User licence and may be reused according to the conditions of the licence. For more details see: http://eprints.nottingham.ac.uk/end_user_agreement.pdf A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.For more information, please contact eprints@nottingham.ac.uk SUMMARYBackground.This study tested the survival efficacy in advanced pancreatic cancer of

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Section: Introductionmentioning

confidence: 99%

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Middleton

Silcocks

Cox

et al. 2014

The Lancet Oncology

312

197

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“…Occasional resistance of PDAC to chemotherapy demanded alternative therapeutic approaches (2,3). An increasing number of novel therapeutic strategies, including targeted therapy or immunotherapy alone or in combination with chemotherapy, have been described but still failed to considerably improve survival times of the patients (4,5).…”

Section: Introductionmentioning

confidence: 99%

Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells

Oberg¹,

Peipp²,

Kellner³

et al. 2014

Cancer Research

124

160

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The ability of human gd T cells from healthy donors to kill pancreatic ductal adenocarcinoma (PDAC) in vitro and in vivo in immunocompromised mice requires the addition of gd T-cell-stimulating antigens. In this study, we demonstrate that gd T cells isolated from patients with PDAC tumor infiltrates lyse pancreatic tumor cells after selective stimulation with phosphorylated antigens. We determined the absolute numbers of gd T-cell subsets in patient whole blood and applied a real-time cell analyzer to measure their cytotoxic effector function over prolonged time periods. Because phosphorylated antigens did not optimally enhance gd T-cell cytotoxicity, we designed bispecific antibodies that bind CD3 or Vg9 on gd T cells and Her2/neu (ERBB2) expressed by pancreatic tumor cells. Both antibodies enhanced gd T-cell cytotoxicity with the Her2/Vg9 antibody also selectively enhancing release of granzyme B and perforin. Supporting these observations, adoptive transfer of gd T cells with the Her2/Vg9 antibody reduced growth of pancreatic tumors grafted into SCID-Beige immunocompromised mice. Taken together, our results show how bispecific antibodies that selectively recruit gd T cells to tumor antigens expressed by cancer cells illustrate the tractable use of endogenous gd T cells for immunotherapy.

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“…Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, with a 5-year survival rate of less than 5% (1). Most patients die within a few months after diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

et al. 2016

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Pancreatic ductal adenocarcinoma (PDAC) is characterized by very early metastasis, suggesting the hypothesis that metastasisassociated changes may occur prior to actual tumor formation. In this study, we identified miR-192 as an epigenetically regulated suppressor gene with predictive value in this disease. miR-192 was downregulated by promoter methylation in both PDAC and chronic pancreatitis, the latter of which is a major risk factor for the development of PDAC. Functional studies in vitro and in vivo in mouse models of PDAC showed that overexpression of miR-192 was sufficient to reduce cell proliferation and invasion. Mechanistic analyses correlated changes in miR-192 promoter methylation and expression with epithelial-mesenchymal transition. Cell proliferation and invasion were linked to altered expression of the miR-192 target gene SERPINE1 that is encoding the protein plasminogen activator inhibitor-1 (PAI-1), an established regulator of these properties in PDAC cells. Notably, our data suggested that invasive capacity was altered even before neoplastic transformation occurred, as triggered by miR-192 downregulation. Overall, our results highlighted a role for miR-192 in explaining the early metastatic behavior of PDAC and suggested its relevance as a target to develop for early diagnostics and therapy.

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New strategies and designs in pancreatic cancer research: consensus guidelines report from a European expert panel

Cited by 73 publications

References 41 publications

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial

Novel Bispecific Antibodies Increase γδ T-Cell Cytotoxicity against Pancreatic Cancer Cells

Early Epigenetic Downregulation of microRNA-192 Expression Promotes Pancreatic Cancer Progression

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