Pancreatic cancer genomes: implications for clinical management and therapeutic development

Dreyer, S. B., Chang, D. K. , Bailey, P. and Biankin, A. V. (2017) Pancreatic cancer genomes: implications for clinical management and therapeutic development. Clinical Cancer Research, 23(7), pp. 1638-1646. (doi:10.1158/1078-0432.CCR-16-2411) (PMID:28373362)

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Abstract

Pancreatic cancer has become the third leading cause of cancer-related death, with little improvement in outcomes despite decades of research. Surgery remains the only chance of cure, yet only 20% of patients will be alive at 5 years after pancreatic resection. Few chemotherapeutics provide any improvement in outcome, and even then, for approved therapies, the survival benefits are marginal. Genomic sequencing studies of pancreatic cancer have revealed a small set of consistent mutations found in most pancreatic cancers and beyond that, a low prevalence for targetable mutations. This may explain the failure of conventional clinical trial designs to show any meaningful survival benefit, except in small and undefined patient subgroups. With the development of next-generation sequencing technology, genomic sequencing and analysis can be performed in a clinically meaningful turnaround time. This can identify therapeutic targets in individual patients and personalize treatment selection. Incorporating preclinical discovery and molecularly guided therapy into clinical trial design has the potential to significantly improve outcomes in this lethal malignancy. In this review, we discuss the findings of recent large-scale genomic sequencing projects in pancreatic cancer and the potential relevance of these data to therapeutic development.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Chang, Dr David and Dreyer, Dr Stephan and Biankin, Professor Andrew and Bailey, Dr Peter
Authors: Dreyer, S. B., Chang, D. K., Bailey, P., and Biankin, A. V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Clinical Cancer Research
Publisher:American Association for Cancer Research
ISSN:1078-0432
ISSN (Online):1557-3265
Published Online:02 April 2017
Copyright Holders:Copyright © 2017 American Association for Cancer Research
First Published:First published in Clinical Cancer Research 23(7): 1638-1646
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656911Defining Platinum and PARP Responsive Molecular Phenotypes of Pancreatic Cancer.Andrew BiankinWellcome Trust (WELLCOME)103721/Z/14/ZICS - TRANSLATIONAL RESEARCH CENTRE
645511Genotype Guided Stratified Therapy for Pancreatic CancerAndrew BiankinCancer Research UK (CAN-RES-UK)17263ICS - TRANSLATIONAL RESEARCH CENTRE
647981CR-UK Centre renewalKaren VousdenCancer Research UK (CAN-RES-UK)18076RI CANCER SCIENCES
712701Clinical Training Award Cycle 2Andrew BiankinCancer Research UK (CAN-RES-UK)20921ICS - TRANSLATIONAL RESEARCH CENTRE
690421Glasgow Molecular Pathology (GMP) NodeKarin OienMedical Research Council (MRC)MR/N005813/1ICS - EXPERIMENTAL THERAPEUTICS