Understanding pancreatic cancer genomes

Cowley, Mark J., Chang, David K., Pajic, Marina, Johns, Amber L., Waddell, Nicola, Grimmond, Sean M. and Biankin, Andrew V. (2013) Understanding pancreatic cancer genomes. Journal of Hepato-Biliary-Pancreatic Sciences, 20 6: 549-556. doi:10.1007/s00534-013-0610-6

Author Cowley, Mark J.
Chang, David K.
Pajic, Marina
Johns, Amber L.
Waddell, Nicola
Grimmond, Sean M.
Biankin, Andrew V.
Title Understanding pancreatic cancer genomes
Journal name Journal of Hepato-Biliary-Pancreatic Sciences   Check publisher's open access policy
ISSN 1868-6974
Publication date 2013-08
Sub-type Article (original research)
DOI 10.1007/s00534-013-0610-6
Volume 20
Issue 6
Start page 549
End page 556
Total pages 8
Place of publication Kudan-kita, Tokyo, Japan
Publisher Springer Japan
Collection year 2014
Language eng
Formatted abstract
Pancreatic cancer is the fourth leading cause of cancer death in our society, with a mortality that virtually parallels its incidence, a median survival of <12 months even with maximal therapy, and a 5-year survival rate of <5 %. The diversity of clinical outcomes and the molecular heterogeneity of histopathologically similar cancer types, incomplete knowledge of the genomic aberrations that drive carcinogenesis and the lack of therapeutics that specifically target most known genomic aberrations necessitates large-scale detailed analysis of cancer genomes to identify novel potential therapeutic strategies. As part of the International Cancer Genome Consortium (ICGC), the Australian Pancreatic Cancer Genome Initiative (APGI) used exomic sequencing and copy number analysis to define genomic aberrations that characterize a large, clinically focused, prospectively accrued cohort of patients with pancreatic cancer. The cohort consisted of early (clinical stages I and II) non-pre-treated patients with pancreatic ductal adenocarcinoma who underwent operative resection with curative intent. We devised approaches to adjust for low epithelial content in primary tumours and to define the genomic landscape of pancreatic cancer to identify novel candidate driver genes and mechanisms. We aim to develop stratified, molecular phenotype-guided therapeutic strategies using existing therapeutics that are either rescued, repurposed, in development, or are known to be effective in an undefined subgroup of PC patients. These are then tested in primary patient-derived xenografts and cell lines from the above deeply characterized cohort. In addition, we return information to treating clinicians that influences patient care and are launching a clinical trial called IMPaCT (Individualized Molecular Pancreatic Cancer Therapy). This umbrella design trial randomizes patients with metastatic disease to either standard first-line therapy with gemcitabine, or a molecular phenotype-guided approach using next-generation sequencing strategies to screen for actionable mutations defined through the ICGC effort.
Keyword Pancreatic cancer
Genome sequencing
Molecular heterogeneity
Functional genomics
Molecular taxonomy
Clinical trial
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 12 times in Thomson Reuters Web of Science Article | Citations
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