Pancreatic Adenocarcinoma: Unconventional Approaches for an Unconventional Disease.

This review highlights current treatments, limitations, and pitfalls in the management of pancreatic cancer and discusses current research in novel targets and drug development to overcome these clinical challenges. We begin with a review of the clinical landscape of pancreatic cancer, including genetic and environmental risk factors, as well as limitations in disease diagnosis and prevention. We next discuss current treatment paradigms for pancreatic cancer and the shortcomings of targeted therapy in this disease. Targeting major driver mutations in pancreatic cancer, such as dysregulation in the KRAS and TGFβ signaling pathways, have failed to improve survival outcomes compared with nontargeted chemotherapy; thus, we describe new advances in therapy such as Ras-binding pocket inhibitors. We then review next-generation approaches in nanomedicine and drug delivery, focusing on preclinical advancements in novel optical probes, antibodies, small-molecule agents, and nucleic acids to improve surgical outcomes in resectable disease, augment current therapies, expand druggable targets, and minimize morbidity. We conclude by summarizing progress in current research, identifying areas for future exploration in drug development and nanotechnology, and discussing future prospects for management of this disease. ©2020 American Association for Cancer Research.