Pancreatic cancer

Pancreatic cancer is highly lethal, with a five-year survival rate of less than 5% [1]. The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDA), accounting for over 250,000 deaths worldwide annually [2] and ranked as the fourth leading cause of cancer mortality in the United States [3]. The poor survival of PDA patients has been attributed to the advanced stage of disease presentation and ineffective therapeutic options. Approximately 20% of PDA patients are diagnosed with localized disease and are candidates for surgical resection with curative intent; however, the majority of these patients unfortunately relapse within several years and carry a five-year post-operative survival of only 20% despite additional treatment with adjuvant chemotherapy [4, 5]. The current worldwide standard treatment for advanced and surgically unresectable pancreatic cancer is the chemotherapeutic agent gemcitabine; however, this intervention only modestly improves patients’ symptoms and has little measurable effect on overall survival [6]. Despite tremendous efforts, only the EGFR inhibitor erlotinib has been approved as an additional agent for PDA patients, albeit for an incremental increase in median overall survival of only two weeks [7]. Therefore the development of new therapeutic approaches for PDA patients that are based upon the underlying biological complexity of this disease is of the utmost importance. The formulation of new treatment strategies for PDA patients requires a detailed understanding of the genetic and epigenetic alterations in PDA tumors and the biochemical signaling networks that are active in this disease. By collectively integrating such information, a multimodal molecular network (MMMN) can be established for PDA and used to probe the biological vulnerabilities of this nefarious malignancy.