Overview of Pancreatic Cancer Biology

Abstract Pancreatic malignancy has been ranked as the fourth major cause of cancer-associated mortality in the United States, and the majority of its pathogenesis can be attributed to three stages of biological development. The inherited and acquired mutations in proto-oncogenes and tumor suppressor genes including KRAS, CDKN2A, Tp53, and SMAD4 lead to the initiation of pancreatic carcinoma. These mutations lead to the formation of a premalignant lesion in the ductal epithelium known as the pancreatic intraepithelial neoplasia (PanIN). The accumulation of incessant mutations leads to further clonal expansion and tumor spread into the local and distant microenvironment owing to its unique features of stromal proliferation and metabolic adaptation to obtain nutrients in a hypoxic environment. Moreover, the presence of a distinctive stem cell compartment is responsible for the rapid spread of the tumor and chemoresistance. An understanding of these molecular alterations along with successive changes in the signal transduction pathways can help in superior comprehension of the underlying molecular biology of pancreatic neoplasms.