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Pancreatic Neoplasms: HELP
Articles by Angelika E. Schnieke
Based on 6 articles published since 2010
(Why 6 articles?)
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Between 2010 and 2020, A. Schnieke wrote the following 6 articles about Pancreatic Neoplasms.
 
+ Citations + Abstracts
1 Review Genetically Engineered Pigs to Study Cancer. 2020

Kalla, Daniela / Kind, Alexander / Schnieke, Angelika. ·Chair of Livestock Biotechnology, School of Life Sciences, Technische Universität München, 85354 Freising, Germany. ·Int J Mol Sci · Pubmed #31940967.

ABSTRACT: Recent decades have seen groundbreaking advances in cancer research. Genetically engineered animal models, mainly in mice, have contributed to a better understanding of the underlying mechanisms involved in cancer. However, mice are not ideal for translating basic research into studies closer to the clinic. There is a need for complementary information provided by non-rodent species. Pigs are well suited for translational biomedical research as they share many similarities with humans such as body and organ size, aspects of anatomy, physiology and pathophysiology and can provide valuable means of developing and testing novel diagnostic and therapeutic procedures. Porcine oncology is a new field, but it is clear that replication of key oncogenic mutation in pigs can usefully mimic several human cancers. This review briefly outlines the technology used to generate genetically modified pigs, provides an overview of existing cancer models, their applications and how the field may develop in the near future.

2 Review Oncogenic KRAS signalling in pancreatic cancer. 2014

Eser, S / Schnieke, A / Schneider, G / Saur, D. ·1] Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany [2] German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · Livestock Biotechnology, Technische Universität München, Liesel-Beckmann Str. 1., 85354 Freising, Germany. · Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany. ·Br J Cancer · Pubmed #24755884.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is almost universally fatal. The annual number of deaths equals the number of newly diagnosed cases, despite maximal treatment. The overall 5-year survival rate of <5% has remained stubbornly unchanged over the last 30 years, despite tremendous efforts in preclinical and clinical science. There is unquestionably an urgent need to further improve our understanding of pancreatic cancer biology, treatment response and relapse, and to identify novel therapeutic targets. Rigorous research in the field has uncovered genetic aberrations that occur during PDAC development and progression. In most cases, PDAC is initiated by oncogenic mutant KRAS, which has been shown to drive pancreatic neoplasia. However, all attempts to target KRAS directly have failed in the clinic and KRAS is widely assumed to be undruggable. This has led to intense efforts to identify druggable critical downstream targets and nodes orchestrated by mutationally activated KRAS. This includes context-specific KRAS effector pathways, synthetic lethal interaction partners and KRAS-driven metabolic changes. Here, we review recent advances in oncogenic KRAS signalling and discuss how these might benefit PDAC treatment in the future.

3 Article A next-generation dual-recombinase system for time- and host-specific targeting of pancreatic cancer. 2014

Schönhuber, Nina / Seidler, Barbara / Schuck, Kathleen / Veltkamp, Christian / Schachtler, Christina / Zukowska, Magdalena / Eser, Stefan / Feyerabend, Thorsten B / Paul, Mariel C / Eser, Philipp / Klein, Sabine / Lowy, Andrew M / Banerjee, Ruby / Yang, Fangtang / Lee, Chang-Lung / Moding, Everett J / Kirsch, David G / Scheideler, Angelika / Alessi, Dario R / Varela, Ignacio / Bradley, Allan / Kind, Alexander / Schnieke, Angelika E / Rodewald, Hans-Reimer / Rad, Roland / Schmid, Roland M / Schneider, Günter / Saur, Dieter. ·Department of Internal Medicine II, Klinikum rechts der Isar, Technische Universität München, München, Germany. · German Cancer Research Center (DKFZ), Division for Cellular Immunology, Heidelberg, Germany. · Gene Center and Department of Biochemistry, Center for Integrated Protein Science CIPSM, Ludwig-Maximilians-Universität München, München, Germany. · Moores Cancer Center, Division of Surgical Oncology, University of California San Diego, La Jolla, California, USA. · Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridge, UK. · Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA. · Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, USA. · Helmholtz Zentrum München, Research Unit Comparative Medicine, Neuherberg, Germany. · MRC Protein Phosphorylation Unit, University of Dundee, Dundee, UK. · Instituto de Biomedicina y Biotecnología de Cantabria (CSIC-UC-Sodercan), Departamento de Biología Molecular, Universidad de Cantabria, Santander, Spain. · Livestock Biotechnology, Technische Universität München, Freising, Germany. · German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany. ·Nat Med · Pubmed #25326799.

ABSTRACT: Genetically engineered mouse models (GEMMs) have dramatically improved our understanding of tumor evolution and therapeutic resistance. However, sequential genetic manipulation of gene expression and targeting of the host is almost impossible using conventional Cre-loxP-based models. We have developed an inducible dual-recombinase system by combining flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies to improve GEMMs of pancreatic cancer. This enables investigation of multistep carcinogenesis, genetic manipulation of tumor subpopulations (such as cancer stem cells), selective targeting of the tumor microenvironment and genetic validation of therapeutic targets in autochthonous tumors on a genome-wide scale. As a proof of concept, we performed tumor cell-autonomous and nonautonomous targeting, recapitulated hallmarks of human multistep carcinogenesis, validated genetic therapy by 3-phosphoinositide-dependent protein kinase inactivation as well as cancer cell depletion and show that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are dispensable for tumor formation.

4 Article Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer. 2013

Eser, Stefan / Reiff, Nina / Messer, Marlena / Seidler, Barbara / Gottschalk, Kathleen / Dobler, Melanie / Hieber, Maren / Arbeiter, Andreas / Klein, Sabine / Kong, Bo / Michalski, Christoph W / Schlitter, Anna Melissa / Esposito, Irene / Kind, Alexander J / Rad, Lena / Schnieke, Angelika E / Baccarini, Manuela / Alessi, Dario R / Rad, Roland / Schmid, Roland M / Schneider, Günter / Saur, Dieter. ·Department of Internal Medicine 2, Technische Universität München, Ismaningerstr. 22, 81675 München, Germany. ·Cancer Cell · Pubmed #23453624.

ABSTRACT: Oncogenic Kras activates a plethora of signaling pathways, but our understanding of critical Ras effectors is still very limited. We show that cell-autonomous phosphoinositide 3-kinase (PI3K) and 3-phosphoinositide-dependent protein kinase 1 (PDK1), but not Craf, are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia (ADM), and pancreatic ductal adenocarcinoma (PDAC) formation. This contrasts with Kras-driven non-small cell lung cancer, where signaling via Craf, but not PDK1, is an essential tumor-initiating event. These in vivo genetic studies together with pharmacologic treatment studies in models of human ADM and PDAC demonstrate tissue-specific differences of oncogenic Kras signaling and define PI3K/PDK1 as a suitable target for therapeutic intervention specifically in PDAC.

5 Article Disclosure of erlotinib as a multikinase inhibitor in pancreatic ductal adenocarcinoma. 2011

Conradt, Laura / Godl, Klaus / Schaab, Christoph / Tebbe, Andreas / Eser, Stefan / Diersch, Sandra / Michalski, Christoph W / Kleeff, Jörg / Schnieke, Angelika / Schmid, Roland M / Saur, Dieter / Schneider, Günter. ·II Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, München, Germany. ·Neoplasia · Pubmed #22131878.

ABSTRACT: A placebo-controlled phase 3 trial demonstrated that the epidermal growth factor receptor (EGFR) inhibitor erlotinib in combination with gemcitabine was especially efficient in a pancreatic ductal adenocarcinoma (PDAC) subgroup of patients developing skin toxicity. However, EGFR expression was not predictive for response, and markers to characterize an erlotinib-responding PDAC group are currently missing. In this work, we observed high erlotinib IC50 values in a panel of human and murine PDAC cell lines. Using EGFR small interfering RNA, we detected that the erlotinib response was marginally influenced by EGFR. To find novel EGFR targets, we used an unbiased chemical proteomics approach for target identification and quality-controlled target affinity determination combined with quantitative mass spectrometry based on stable isotope labeling by amino acids in cell culture. In contrast to gefitinib, we observed a broad target profile of erlotinib in PDAC cells by quantitative proteomics. Six protein kinases bind to erlotinib with similar or higher affinity (K(d) = 0.09-0.358 µM) than the EGFR (K(d) 0.434 µM). We provide evidence that one of the novel erlotinib targets, ARG, contributes in part to the erlotinib response in a PDAC cell line. Our data show that erlotinib is a multikinase inhibitor, which can act independent of EGFR in PDAC. These findings may help to monitor future erlotinib trials in the clinic.

6 Article In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging. 2011

Eser, Stefan / Messer, Marlena / Eser, Philipp / von Werder, Alexander / Seidler, Barbara / Bajbouj, Monther / Vogelmann, Roger / Meining, Alexander / von Burstin, Johannes / Algül, Hana / Pagel, Philipp / Schnieke, Angelika E / Esposito, Irene / Schmid, Roland M / Schneider, Günter / Saur, Dieter. ·II Medizinische Klinik, Technische Universität München, 81675 Munich, Germany. ·Proc Natl Acad Sci U S A · Pubmed #21628592.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC.