Neoplasms of the Exocrine Pancreas

Abstract

OverviewAdenocarcinoma of the pancreas is one of the most morbid and lethal malignancies. Worldwide, it accounts for 330,000 deaths annually. Smoking and obesity are both risk factors for pancreatic cancer and current estimates suggest half of all cases may be preventable. Genetic predisposition to pancreatic cancer is associated with some genetic syndromes to include BRCA1 or BRCA2 germline mutations, Peutz–Jeghers syndrome, and hereditary nonpolyposis colon cancer. Somatic mutations in KRAS, CDKN2A/INK4A, TP53, and SMAD4/DPC4 are common. Pancreatic cancer is often diagnosed when the primary tumor is inoperable or there is metastatic spread rendering the cancer incurable. At present, clinical staging defines the malignancy as resectable (and potentially curable), borderline resectable, locally advanced, or metastatic. Surgery with curative intent is possible for patients with resectable disease and for a subset of patients with borderline resectable disease. While chemotherapy has been proved to prolong survival as a component of adjuvant therapy, and as therapy for locally advanced or metastatic disease, the role of radiation therapy in treatment is less‐well defined and not universally accepted. Thus far, molecular targeted therapy has shown no clinically meaningful benefit. Adjuvant and neoadjuvant approaches are employed in patients with resectable and borderline resectable disease. Intense research in the molecular biology of pancreatic cancer continues with increasing interest in the role of the tumor microenvironment in invasion, metastatic potential, and resistance. Novel therapeutic strategies that focus on stromal modification and immunologic manipulation are at the forefront of clinical and translational research efforts.