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Pancreatic Cancer Genomes: Implications for Clinical Management and Therapeutic Development
Stephan B Dreyer1,2, David K Chang1,2, Peter Bailey1
1Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Bearsden, Glasgow, Scotland, United Kingdom.
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. Clin Cancer Res; 23(7); 1638-46. ©2017 AACRSee all articles in this CCR Focus section, "Pancreatic Cancer: Challenge and Inspiration."
Insights
Pancreatic cancer has poor outcomes. Genomic sequencing identifies potential therapeutic targets, offering hope for personalized treatments and improved survival rates in this lethal malignancy.
Area of Science:
- Oncology
- Genomics
- Translational Research
Background:
- Pancreatic cancer is a leading cause of cancer death with limited treatment options.
- Current therapies offer marginal survival benefits, and only 20% of patients survive 5 years post-surgery.
- Genomic studies reveal few targetable mutations, explaining challenges in clinical trials.
Purpose of the Study:
- To review findings from large-scale genomic sequencing projects in pancreatic cancer.
- To discuss the relevance of genomic data for therapeutic development.
- To highlight the potential of personalized, molecularly guided therapies.
Main Methods:
- Analysis of large-scale genomic sequencing data from pancreatic cancer patients.
- Review of recent preclinical discoveries and molecularly guided therapeutic strategies.
- Discussion of next-generation sequencing technology for rapid genomic analysis.
Main Results:
- Genomic sequencing reveals consistent mutations in pancreatic cancer.
- A low prevalence of targetable mutations has been observed.
- Next-generation sequencing enables timely identification of therapeutic targets for individual patients.
Conclusions:
- Personalized treatment selection based on genomic profiling can improve outcomes.
- Incorporating molecularly guided therapy into clinical trials is crucial.
- Genomic insights hold significant potential for advancing pancreatic cancer treatment.