TY  - JOUR
A1  - Biederstädt, Alexander
A1  - Hassan, Zonera
A1  - Schneeweis, Christian
A1  - Schick, Markus
A1  - Schneider, Lara
A1  - Muckenhuber, Alexander
A1  - Hong, Yingfen
A1  - Siegers, Gerrit
A1  - Nilsson, Lisa
A1  - Wirth, Matthias
A1  - Dantes, Zahra
A1  - Steiger, Katja
A1  - Schunck, Kathrin
A1  - Langston, Steve
A1  - Lenhof, Hans-Peter
A1  - Coluccio, Andrea
A1  - Orben, Felix
A1  - Slawska, Jolanta
A1  - Scherger, Anna
A1  - Saur, Dieter
A1  - Müller, Stefan
A1  - Rad, Roland
A1  - Weichert, Wilko
A1  - Nilsson, Jonas
A1  - Reichert, Maximilian
A1  - Schneider, Günter
A1  - Keller, Ulrich
T1  - SUMO pathway inhibition targets an aggressive pancreatic cancer subtype
T2  - Gut
N2  - Objective: Pancreatic ductal adenocarcinoma (PDAC) still carries a dismal prognosis with an overall 5-year survival rate of 9%. Conventional combination chemotherapies are a clear advance in the treatment of PDAC; however, subtypes of the disease exist, which exhibit extensive resistance to such therapies. Genomic MYC amplifications represent a distinct subset of PDAC with an aggressive tumour biology. It is clear that hyperactivation of MYC generates dependencies that can be exploited therapeutically. The aim of the study was to find and to target MYC-associated dependencies.
Design: We analysed human PDAC gene expression datasets. Results were corroborated by the analysis of the small ubiquitin-like modifier (SUMO) pathway in a large PDAC cohort using immunohistochemistry. A SUMO inhibitor was used and characterised using human and murine two-dimensional, organoid and in vivo models of PDAC.
Results: We observed that MYC is connected to the SUMOylation machinery in PDAC. Components of the SUMO pathway characterise a PDAC subtype with a dismal prognosis and we provide evidence that hyperactivation of MYC is connected to an increased sensitivity to pharmacological SUMO inhibition.
Conclusion: SUMO inhibitor-based therapies should be further developed for an aggressive PDAC subtype.
KW  - cancer
KW  - pancreatic cancer
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/53079
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-530798
SN  - 1468-3288
SN  - 0017-5749
N1  - This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
VL  - 0
SP  - 1
EP  - 11
PB  - BMJ Publishing Group
CY  - London
ER  -