Pancreatic cancer genomics.
Pancreatic cancer is one of the most lethal malignancies. The overall median survival even with treatment is only 6-9 months, with almost 90% succumbing to the disease within a year of diagnosis. It is characterised by an intense desmoplastic stroma that may contribute to therapeutic resistance, and poses significant challenges for genomic sequencing studies. It is recalcitrant to almost all therapies and consequently remains the fourth leading cause of cancer death in Western societies. Genomic studies are unveiling a vast heterogeneity of mutated genes, and this diversity may explain why conventional clinical trial designs have mostly failed to demonstrate efficacy in unselected patients. Those that are available offer only marginal benefits overall, but are associated with clinically significant responses in as yet undefined subgroups. This chapter describes our current understanding of the genomics of pancreatic cancer and the potential impact of these findings on our approaches to treatment.
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland G4 0SF, United Kingdom; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW 2200, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, NSW 2170, Australia.
David K
DK
Chang
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom; Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD, Australia. Electronic address: s.grimmond@imb.uq.edu.au.
Sean M
SM
Grimmond
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow, Scotland G61 1BD, United Kingdom; West of Scotland Pancreatic Unit, Glasgow Royal Infirmary, Glasgow, Scotland G4 0SF, United Kingdom; The Kinghorn Cancer Centre, Cancer Division, Garvan Institute of Medical Research, 370 Victoria Street, Darlinghurst, Sydney, NSW 2010, Australia; St Vincent's Clinical School, Faculty of Medicine, University of NSW, Australia; Department of Surgery, Bankstown Hospital, Eldridge Road, Bankstown, Sydney, NSW 2200, Australia; South Western Sydney Clinical School, Faculty of Medicine, University of NSW, Liverpool, NSW 2170, Australia. Electronic address: sean.grimmond@glasgow.ac.uk.
Andrew V
AV
Biankin
D000818:Animals; D023281:Genomics; D005838:Genotype; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D010641:Phenotype; D057285:Precision Medicine