Explore the words cloud of the PanCaT project. It provides you a very rough idea of what is the project "PanCaT" about.
The following table provides information about the project.
KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN
|Coordinator Country||Germany [DE]|
|Total cost||2˙440˙275 €|
|EC max contribution||2˙440˙275 € (100%)|
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
|Duration (year-month-day)||from 2016-02-01 to 2021-01-31|
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|1||KLINIKUM RECHTS DER ISAR DER TECHNISCHEN UNIVERSITAT MUNCHEN||DE (MUENCHEN)||coordinator||2˙440˙275.00|
Maintenance and drug resistance of pancreatic ductal adenocarcioma (PDAC) depends on cancer cell intrinsic mechanisms and a stroma that supports tumor growth. Mouse models of human PDAC have provided important insights into the evolution of this highly lethal tumor, but there are no models that allow secondary genetic manipulation of autochthonous tumors, the tumor microenvironment or the metastatic host niche once the tumor has formed.
We generated an inducible dual-recombinase system by combining Flp/frt and Cre/loxP. This novel PDAC model permits spatial and temporal control of gene expression enabling unbiased genetic approaches to study the role of tumor cell-autonomous and non-autonomous functions in endogenous cancers. This tool provides unparalleled access to the native biology of cancer cells and their hosting stroma, and rigorous genetic validation of candidate therapeutic targets. We performed tumor cell-autonomous and non-autonomous targeting, uncovered hallmarks of human multistep carcinogenesis, validated genetic tumor therapy, and showed that mast cells in the tumor microenvironment, which had been thought to be key oncogenic players, are in fact dispensable for tumor formation.
In the proposed research program, we will 1) develop and further improve next-generation PDAC models, 2) deploy these systems to identify and target key features of PDAC maintenance in tumor cells and their microenvironment, and 3) discover mechanisms of treatment resistance. The application of cutting edge genetic engineering and screening technologies will allow us to address biological questions that could not be addressed before. The PanCaT project will open new horizons for the functional understanding of pancreatic cancer biology with a strong impact on clinical management and prognosis of PDAC patients. It will also produce a unique set of highly versatile and widely applicable genetic tools that will facilitate the study of PDAC at an organismal level.
|year||authors and title||journal||last update|
Roman Maresch, Sebastian Mueller, Christian Veltkamp, Rupert Ã–llinger, Mathias Friedrich, Irina Heid, Katja Steiger, Julia Weber, Thomas Engleitner, Maxim Barenboim, Sabine Klein, Sandra Louzada, Ruby Banerjee, Alexander Strong, Teresa Stauber, Nina Gross, Ulf Geumann, Sebastian Lange, Marc Ringelhan, Ignacio Varela, Kristian Unger, Fengtang Yang, Roland M. Schmid, George S. Vassiliou, Rickmer Braren, GÃ¼nter Schneider, Mathias Heikenwalder, Allan Bradley, Dieter Saur, Roland Rad
Multiplexed pancreatic genome engineering and cancer induction by transfection-based CRISPR/Cas9 delivery in mice
published pages: 10770, ISSN: 2041-1723, DOI: 10.1038/ncomms10770
|Nature Communications 7||2019-06-06|
GÃ¼nter Schneider, Marc Schmidt-Supprian, Roland Rad, Dieter Saur
Tissue-specific tumorigenesis: context matters
published pages: 239-253, ISSN: 1474-175X, DOI: 10.1038/nrc.2017.5
|Nature Reviews Cancer 17/4||2019-06-06|
Sebastian Mueller, Thomas Engleitner, Roman Maresch, Magdalena Zukowska, Sebastian Lange, Thorsten Kaltenbacher, BjÃ¶rn Konukiewitz, Rupert Ã–llinger, Maximilian Zwiebel, Alex Strong, Hsi-Yu Yen, Ruby Banerjee, Sandra Louzada, Beiyuan Fu, Barbara Seidler, Juliana GÃ¶tzfried, Kathleen Schuck, Zonera Hassan, Andreas Arbeiter, Nina SchÃ¶nhuber, Sabine Klein, Christian Veltkamp, Mathias Friedrich, Lena Rad, Maxim Barenboim, Christoph Ziegenhain, Julia Hess, Oliver M. Dovey, Stefan Eser, Swati Parekh, Fernando Constantino-Casas, Jorge de la Rosa, Marta I. Sierra, Mario Fraga, Julia Mayerle, GÃ¼nter KlÃ¶ppel, Juan CadiÃ±anos, Pentao Liu, George Vassiliou, Wilko Weichert, Katja Steiger, Wolfgang Enard, Roland M. Schmid, Fengtang Yang, Kristian Unger, GÃ¼nter Schneider, Ignacio Varela, Allan Bradley, Dieter Saur, Roland Rad
Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes
published pages: 62-68, ISSN: 0028-0836, DOI: 10.1038/nature25459
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