New Developments in the Molecular Mechanisms of Pancreatic Tumorigenesis

Pancreatic cancer is an aggressive disease with a dismal prognosis in dire need of novel diagnostic and therapeutic approaches. The past decade has witnessed an explosion of data on the genetic alterations that occur in pancreatic cancer, as comprehensive next-generation sequencing analyses have been performed on samples from large cohorts of patients. These studies have defined the genomic landscape of this disease and identified novel candidates whose mutations contribute to pancreatic tumorigenesis. They have also clarified the genetic alterations that underlie multistep tumorigenesis in precursor lesions and provided insights into clonal evolution in pancreatic neoplasia. In addition to these important insights into pancreatic cancer biology, these large scale genomic studies have also provided a foundation for the development of novel early detection strategies and targeted therapies. In this review, we discuss the results of these comprehensive sequencing studies of pancreatic neoplasms, with a particular focus on how their results will impact the clinical care of patients with pancreatic cancer.