Precision medicine based on next-generation sequencing and master controllers

Despite decades of research and efforts at improving survival, pancreatic ductal adenocarcinoma (PDA) has become the third leading cause of cancer-related deaths in the United States. In fact, by 2020, it is projected to become the second leading cause of cancer-related deaths in the United States. Personalized, or precision, medicine has resulted in improving patient outcomes in other tumor systems. However, for pancreatic cancer patients, there are a limited number of evidence-based targeted therapeutic options that are currently available. Significant advances in DNA sequencing technology have resulted in the identification of a number of genetic mutations and the delineation of core signaling pathways important in PDA. This has subsequently resulted in an advanced understanding of the genetic drivers of the progression of this disease. Facile sequencing technology has moved the field closer to a personalized approach to treating pancreatic cancer. Improvements to the personalized therapy approach will likely result from several factors including the delivery of tumor sequencing results in a clinically relevant timeframe, the development of better targeted drugs, and perhaps a molecular-targeted approach to aspects of PDA biology beyond mutations in the deoxyribonucleic acid (DNA). These advances will allow clinicians to enroll patients in appropriate-matched clinical trials in a timely manner. In this chapter, the opportunities and limitations of a targeted, personalized approach to treating PDA will be discussed.