Systems Biology of Pancreatic Cancer: The Role of Tumor-Microenvironment Communication in Development, Progression and Therapy Resistance

Abstract

Pancreatic cancer is an aggressive and highly lethal disease, with a reported 5-year survival of ∼5 %. It comprises the fourth most common cause of malignancy-related death in Western countries and the annual death rate due to this disease approximates its annual incidence rate, which is estimated to be ∼10 cases per 100,000 population. Although there have been some advancements in surgical techniques and adjuvant therapeutic regimens, the survival has not substantially improved in the past 30 years. Pancreatic cancer is characterized by late diagnosis, aggressive local invasion, early systemic dissemination and resistance to chemo- and radiotherapy. Therefore, a better understanding of cellular and molecular mechanisms governing the resistant phenotype of this devastating disease is urgently needed. Systems biology has emerged as one of the most promising approaches to understand the complexities of tumor-microenvironment interplay on a quantitative multi-scale level, i.e. by incorporating genomics, transcriptomics, proteomics, epigenomics and functional genomics studies. Integrative analysis of these data aims to dissect inter- and intracellular networks critically contributing to tumor progression and therapy resistance.