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Clin Ther. 2016 Jul;38(7):1622-35. doi: 10.1016/j.clinthera.2016.03.006. Epub 2016 Apr 1.

Genetic Testing in Pancreatic Ductal Adenocarcinoma: Implications for Prevention and Treatment.

Author information

1
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. Electronic address: mbpeters@bidmc.harvard.edu.
2
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
3
Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Abstract

PURPOSE:

This article reviews the progress to date and future directions for investigation of germline and somatic genetic testing to inform pancreatic adenocarcinoma (PDAC) treatment, screening, and prevention strategies.

METHODS:

We searched PubMed to identify recent articles regarding genetic testing in pancreatic cancer, including both germline and somatic testing, and recent genome-wide association studies. References were specifically hand searched as relevant. Guidelines for testing and screening high-risk individuals were included. We searched clinicaltrials.gov to review the current landscape of active clinical trials.

FINDINGS:

Approximately 10% of PDACs are associated with an identified germline mutation. Although germline mutations may inform treatment options and identify high-risk individuals for screening in other cancers, the data on PDAC are only now emerging. For example, poly adenosine diphosphate ribose polymerase (PARP) inhibitors are under investigation for BRCA-associated PDAC. Somatic mutations have also been identified in PDAC. However, current data are limited regarding treatment for potential PDAC somatic driver mutations. Although erlotinib is used in PDAC, its use is not targeted based on a tumor marker. Many tyrosine kinase inhibitors targeted toward potential driver mutations and critical pathways are in development, including BRAF/MEK, ALK, and CDK4/6. A consensus on screening strategies for individuals at high risk for PDAC is still evolving because of the relatively low prevalence of the disease, the relative invasiveness of endoscopic procedures often used as part of screening, and the lack of a clear survival benefit.

IMPLICATIONS:

Pancreatic cancer has been slower to move toward genomic testing, partially because of a lower prevalence of mutations and partially because of a limited effect of results on treatment choices outside a clinical trial. This is an area of active investigation, and we anticipate that there will be both preventive and therapeutic implications of driver mutations in the coming decade.

KEYWORDS:

genetic testing; germline mutation; pancreatic ductal adenocarcinoma; somatic mutation

PMID:
27041411
DOI:
10.1016/j.clinthera.2016.03.006
[Indexed for MEDLINE]

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