Journal article

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Stephan B Dreyer, Rosie Upstill-Goddard, Viola Paulus-Hock, Clara Paris, Eirini-Maria Lampraki, Eloise Dray, Bryan Serrels, Giuseppina Caligiuri, Selma Rebus, Dennis Plenker, Zachary Galluzzo, Holly Brunton, Richard Cunningham, Mathias Tesson, Craig Nourse, Ulla-Maja Bailey, Marc Jones, Kim Moran-Jones, Derek W Wright, Fraser Duthie Show all



BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and h..

View full abstract


Awarded by National Health and Medical Research Council of Australia

Awarded by Cancer Council New South Wales (NSW)

Awarded by Cancer Institute NSW

Awarded by National Institutes of Health grants

Awarded by Cancer Research UK

Awarded by Wellcome Trust

Awarded by Pancreatic Cancer UK Future Research Leaders Fund

Awarded by Scottish Genome Partnership

Awarded by Italian Cancer Genome Project-Ministry of University

Awarded by Associazione Italiana Ricerca Cancro

Awarded by FP7 European Community Grant Cam-Pac

Awarded by Italian Ministry of Health

Funding Acknowledgements

This work was supported by the National Health and Medical Research Council of Australia (631701, 535903, 427601); Queensland Government National and International Research Alliances Program (NIRAP); University of Queensland; Institute for Molecular Bioscience; Australian Government: Department of Innovation, Industry, Science and Research; Australian Cancer Research Foundation; Cancer Council New South Wales (NSW) (SRP06-01, SRP11-01.ICGC); Cancer Institute NSW (10/ECF/2-26, 06/ECF/1-24, 09/CDF/2-40, 07/CDF/1-03, 10/CRF/1-01, 08/RSA/1-15, 07/CDF/1-28, 10/CDF/2-26,10/FRL/2-03, 06/RSA/1-05, 09/RIG/1-02, 10/TPG/1-04, 11/REG/1-10, 11/CDF/3-26); Garvan Institute of Medical Research; Avner Nahmani Pancreatic Cancer Research Foundation; R. T. Hall Trust; Petre Foundation; Philip Hemstritch Foundation; Gastroenterological Society of Australia; American Association for Cancer Research; Landon Foundation-INNOVATOR Award; Royal Australasian College of Surgeons; Royal Australasian College of Physicians; Royal College of Pathologists of Australasia; Susan Wojcicki and Dennis Tropper; National Institutes of Health grants CA62924, 5R01CA150190-07, and P50 CA102701; Cancer Research UK C29717/A17263, C29717/A18484, C596/A18076, C596/A20921, and A23526; Wellcome Trust Senior Investigator Award 103721/Z/14/Z; Pancreatic Cancer UK Future Research Leaders Fund FLF2015_04_Glasgow; Scottish Genome Partnership SEHHD-CSO 1175759/2158447; MRC/EPSRC Glasgow Molecular Pathology Node; The Howat Foundation; Italian Cancer Genome Project-Ministry of University (FIRB RBAP10AHJB); Associazione Italiana Ricerca Cancro (grant no. 12182); FP7 European Community Grant Cam-Pac (no. 602783); Italian Ministry of Health (FIMP-CUP_J33G13000210001); and International Cancer Genome Consortium, Ontario Institute for Cancer Research.