Abstract
Current standard-of-care for patients with pancreatic ductal adenocarcinoma (PDAC) focusses on chemotherapeutic regimens and pancreatic cancer surgery. However, limited treatment options, late diagnosis in advanced tumor stages and the aggressive behavior of PDAC contribute to the high mortality of the disease. Consequently, there is an urgent need of precision medicine for pancreatic cancer patients. All over the world, numerous initiatives started in recent years to translate novel scientific discoveries into prospective clinical trials. One major approach pursues the stratification of PDAC patients according the tumor transcriptome to predict treatment response. Other strategies concentrate on genomic alterations and the identification of individualized targeted therapies. Further experimental studies are ongoing to detect novel biomarkers for cancer diagnosis, subtyping, treatment response prediction or clinical outcome. However, the challenge remains to transfer the knowledge into clinical practice. In this review, we summarize current literature and knowledge and highlight novel concepts of basic and clinical research uncovering suitable biomarkers and targeted therapies. Thus, we provide an overview of preclinical and clinical efforts of precision medicine in pancreatic cancer.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of cancer in the pancreas and is burdened with a poor prognosis
Different research groups identified pancreatic cancer subclasses based on alterations in gene expression that are associated with tumor grade, survival rate and therapy response
We could show that the immune microenvironment in pancreatic ductal adenocarcinoma (PDAC) can be of prognostic value and we provided a signature comprising different leukocyte subpopulations and stromal composition to stratify patients using progression free survival as the primary outcome [34]
Summary
Pancreatic ductal adenocarcinoma (PDAC) is the most common type of cancer in the pancreas and is burdened with a poor prognosis. Further strategies of targeting actionable mutations are ongoing (see review from Nevala-Plagemann [24]); a prospective proof of effectiveness and performance for biomarker-selected therapies remains to be confirmed in pancreatic cancer patients Another approach for stratifying pancreatic cancer patients utilizes transcriptomic changes of the tumor tissue (Figure 1). Different research groups identified pancreatic cancer subclasses based on alterations in gene expression that are associated with tumor grade, survival rate and therapy response. The molecular profiling of Moffitt et al in 2015 distinguished between a classical and basal-like PDAC subtype and they detected a significantly decreased overall survival for the basal-like subtype They virtually separated the transcriptome of the fibroinflammatory compartment from the tumor and identified a silent and activated stroma signature. Several worldwide initiatives focus on how to implement the stratification approaches in personalized treatment decisions and clinical management of PDAC patients
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