Systems Biology Approaches to Pancreatic Cancer Detection, Prevention and Treatment

Abstract

Pancreatic cancer [PC] is a complex disease harboring multiple genetic alterations. It is now well known that deregulation in the expression and function of oncogenes and tumor suppressor genes contributes to the development and progression of PC. The last 40 years have not seen any major improvements in the dismal overall cure rate for PC where drug resistance is an emerging and recurring obstacle for successful treatment of PC. Additionally, the lack of molecular biomarkers for patient selection limits drug availabilities for tailored therapy for patients diagnosed with PC. The very high failure rate of new drugs in Phase III clinical trials in PC calls for a more robust pre-clinical and clinical testing of new compounds. In order to rationally choose combinations of targeted agents that may improve therapeutic outcome by overcoming drug resistance, one needs to apply newer research tools such as systems and network biology. These newer tools are expected to assist in the design of effective drug combinations for the treatment of PC and are expected to become an important part in any future clinical trials. In this review we will provide background information on the current state of PC research, the reasons for drug failure and how to overcome these issues using systems sciences. We conclude this review with an example on how systems and network methodologies can help in the design efficacious drug combinations for this deadly and by far incurable disease.

The Aurora-A–Twist1 axis promotes highly aggressive phenotypes in pancreatic carcinoma

“…Pancreatic ductal adenocarcinoma (PDAC) is an exceptionally aggressive disease (Alian et al, 2014). Accumulating evidence suggests that the acquisition of epithelial-to-mesenchymal transition (EMT) phenotypes in pancreatic tumors is an important underlying cause for extensive tumor invasion, early metastasis, drug resistance and tumor recurrence (Castellanos et al, 2013).…”

Phosphorylation-dependent regulation of ALDH1A1 by Aurora kinase A: insights on their synergistic relationship in pancreatic cancer

“…Pancreatic cancer is an exceptionally aggressive disease with the majority of its victims dying within 1 year of diagnosis [ 1 ]. Effective early detection and screening are not available, and tumors are typically diagnosed after metastasis.…”

Current State of “Omics” Biomarkers in Pancreatic Cancer

“…Therefore, not only genomics biomarkers but also network reconstructions [ 33 ], including different omics levels, become an essential tool for exploring the disease under the systems biology perspective. Network models and computational platforms for integrating and analyzing these data, as well as investigating more thoroughly into these networks by simulations, are prominent efforts.…”