MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies

被引:104
作者
Hessmann, E. [1 ]
Schneider, G. [2 ]
Ellenrieder, V. [1 ]
Siveke, J. T. [2 ,3 ,4 ]
机构
[1] Univ Med Ctr Goettingen, Clin Gastroenterol & Gastrointestinal Oncol, Gottingen, Germany
[2] Tech Univ Munich, Klinikum Rechts Isar, Dept Internal Med 2, Med Klin, D-80290 Munich, Germany
[3] German Canc Consortium DKTK, Heidelberg, Germany
[4] German Canc Res Ctr, Heidelberg, Germany
关键词
BET BROMODOMAIN INHIBITION; SMALL-MOLECULE INHIBITORS; C-MYC; GENE-EXPRESSION; DUCTAL ADENOCARCINOMA; N-MYC; TRANSCRIPTIONAL ACTIVATION; POTENTIAL TARGET; TRANSGENIC MICE; TUMOR;
D O I
10.1038/onc.2015.216
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches.
引用
收藏
页码:1609 / 1618
页数:10
相关论文
共 139 条
[1]   Origin of pancreatic ductal adenocarcinoma from atypical flat lesions: a comparative study in transgenic mice and human tissues [J].
Aichler, Michaela ;
Seiler, Christopher ;
Tost, Monica ;
Siveke, Jens ;
Mazur, Pawel K. ;
Da Silva-Buttkus, Patricia ;
Bartsch, Detlef K. ;
Langer, Peter ;
Chiblak, Sara ;
Duerr, Anna ;
Hoefler, Heinz ;
Kloeppel, Guenter ;
Mueller-Decker, Karin ;
Brielmeier, Markus ;
Esposito, Irene .
JOURNAL OF PATHOLOGY, 2012, 226 (05) :723-734
[2]   Signatures of mutational processes in human cancer [J].
Alexandrov, Ludmil B. ;
Nik-Zainal, Serena ;
Wedge, David C. ;
Aparicio, Samuel A. J. R. ;
Behjati, Sam ;
Biankin, Andrew V. ;
Bignell, Graham R. ;
Bolli, Niccolo ;
Borg, Ake ;
Borresen-Dale, Anne-Lise ;
Boyault, Sandrine ;
Burkhardt, Birgit ;
Butler, Adam P. ;
Caldas, Carlos ;
Davies, Helen R. ;
Desmedt, Christine ;
Eils, Roland ;
Eyfjord, Jorunn Erla ;
Foekens, John A. ;
Greaves, Mel ;
Hosoda, Fumie ;
Hutter, Barbara ;
Ilicic, Tomislav ;
Imbeaud, Sandrine ;
Imielinsk, Marcin ;
Jaeger, Natalie ;
Jones, David T. W. ;
Jones, David ;
Knappskog, Stian ;
Kool, Marcel ;
Lakhani, Sunil R. ;
Lopez-Otin, Carlos ;
Martin, Sancha ;
Munshi, Nikhil C. ;
Nakamura, Hiromi ;
Northcott, Paul A. ;
Pajic, Marina ;
Papaemmanuil, Elli ;
Paradiso, Angelo ;
Pearson, John V. ;
Puente, Xose S. ;
Raine, Keiran ;
Ramakrishna, Manasa ;
Richardson, Andrea L. ;
Richter, Julia ;
Rosenstiel, Philip ;
Schlesner, Matthias ;
Schumacher, Ton N. ;
Span, Paul N. ;
Teague, Jon W. .
NATURE, 2013, 500 (7463) :415-+
[3]   Immunology in the clinic review series; focus on cancer: multiple roles for the immune system in oncogene addiction [J].
Bachireddy, P. ;
Rakhra, K. ;
Felsher, D. W. .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2012, 167 (02) :188-194
[4]   Both p16Ink4a and the p19Arf-p53 pathway constrain progression of pancreatic adenocarcinoma in the mouse [J].
Bardeesy, N ;
Aguirre, AJ ;
Chu, GC ;
Cheng, KH ;
Lopez, LV ;
Hezel, AF ;
Feng, B ;
Brennan, C ;
Weissleder, R ;
Mahmood, U ;
Hanahan, D ;
Redston, MS ;
Chin, L ;
DePinho, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (15) :5947-5952
[5]   c-Myc phosphorylation is required for cellular response to oxidative stress [J].
Benassi, B ;
Fanciulli, M ;
Fiorentino, F ;
Porrello, A ;
Chiorino, G ;
Loda, M ;
Zupi, G ;
Biroccio, A .
MOLECULAR CELL, 2006, 21 (04) :509-519
[6]   Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes [J].
Biankin, Andrew V. ;
Waddell, Nicola ;
Kassahn, Karin S. ;
Gingras, Marie-Claude ;
Muthuswamy, Lakshmi B. ;
Johns, Amber L. ;
Miller, David K. ;
Wilson, Peter J. ;
Patch, Ann-Marie ;
Wu, Jianmin ;
Chang, David K. ;
Cowley, Mark J. ;
Gardiner, Brooke B. ;
Song, Sarah ;
Harliwong, Ivon ;
Idrisoglu, Senel ;
Nourse, Craig ;
Nourbakhsh, Ehsan ;
Manning, Suzanne ;
Wani, Shivangi ;
Gongora, Milena ;
Pajic, Marina ;
Scarlett, Christopher J. ;
Gill, Anthony J. ;
Pinho, Andreia V. ;
Rooman, Ilse ;
Anderson, Matthew ;
Holmes, Oliver ;
Leonard, Conrad ;
Taylor, Darrin ;
Wood, Scott ;
Xu, Qinying ;
Nones, Katia ;
Fink, J. Lynn ;
Christ, Angelika ;
Bruxner, Tim ;
Cloonan, Nicole ;
Kolle, Gabriel ;
Newell, Felicity ;
Pinese, Mark ;
Mead, R. Scott ;
Humphris, Jeremy L. ;
Kaplan, Warren ;
Jones, Marc D. ;
Colvin, Emily K. ;
Nagrial, Adnan M. ;
Humphrey, Emily S. ;
Chou, Angela ;
Chin, Venessa T. ;
Chantrill, Lorraine A. .
NATURE, 2012, 491 (7424) :399-405
[7]   TGF-β and cancer [J].
Bierie, B ;
Moses, HL .
CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (1-2) :29-40
[8]   Genome Profiling of Pancreatic Adenocarcinoma [J].
Birnbaum, David J. ;
Adelaide, Jose ;
Mamessier, Emilie ;
Finetti, Pascal ;
Lagarde, Arnaud ;
Monges, Genevieve ;
Viret, Frederic ;
Goncalves, Anthony ;
Turrini, Olivier ;
Delpero, Jean-Robert ;
Iovanna, Juan ;
Giovannini, Marc ;
Birnbaum, Daniel ;
Chaffanet, Max .
GENES CHROMOSOMES & CANCER, 2011, 50 (06) :456-465
[9]   Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription [J].
Bisgrovet, Dwayne A. ;
Mahmoudi, Tokameh ;
Henklein, Peter ;
Verdin, Eric .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (34) :13690-13695
[10]   Organoid Models of Human and Mouse Ductal Pancreatic Cancer [J].
Boj, Sylvia F. ;
Hwang, Chang-Il ;
Baker, Lindsey A. ;
Chio, Iok In Christine ;
Engle, Dannielle D. ;
Corbo, Vincenzo ;
Jager, Myrthe ;
Ponz-Sarvise, Mariano ;
Tiriac, Herve ;
Spector, Mona S. ;
Gracanin, Ana ;
Oni, Tobiloba ;
Yu, Kenneth H. ;
van Boxtel, Ruben ;
Huch, Meritxell ;
Rivera, Keith D. ;
Wilson, John P. ;
Feigin, Michael E. ;
Oehlund, Daniel ;
Handly-Santana, Abram ;
Ardito-Abraham, Christine M. ;
Ludwig, Michael ;
Elyada, Ela ;
Alagesan, Brinda ;
Biffi, Giulia ;
Yordanov, Georgi N. ;
Delcuze, Bethany ;
Creighton, Brianna ;
Wright, Kevin ;
Park, Youngkyu ;
Morsink, Folkert H. M. ;
Molenaar, I. Quintus ;
Rinkes, Inne H. Borel ;
Cuppen, Edwin ;
Hao, Yuan ;
Jin, Ying ;
Nijman, Isaac J. ;
Iacobuzio-Donahue, Christine ;
Leach, Steven D. ;
Pappin, Darryl J. ;
Hammell, Molly ;
Klimstra, David S. ;
Basturk, Olca ;
Hruban, Ralph H. ;
Offerhaus, George Johan ;
Vries, Robert G. J. ;
Clevers, Hans ;
Tuveson, David A. .
CELL, 2015, 160 (1-2) :324-338