Pancreatic ductal adenocarcinoma (PDAC) is the fourth highest cause of cancer-related deaths in the United States, and for the vast majority of patients chemotherapy is the only course of treatment. The recent use FOLFIRINOX has provided the most significant survival benefit (~4 months) of any treatment brought to the clinic in nearly two decades. Despite recent advances, chemotherapeutics have proven woefully inadequate to treat this cancer. One of the hallmarks of PDAC is the presence of an extensive desmoplastic reaction consisting of pancreatic stellate cells, fibroblasts, immune cells, vasculature, and extracellular matrix. The complex interaction between cancer cells and the tumor microenvironment in PDAC is beginning to be understood, and the disruption of these interactions is a promising new avenue for therapeutic targeting of PDAC. In this chapter we will discuss a variety of therapies now entering the clinic that specifically target the tumor stroma. Among these are therapies that reduce the tumor stroma, allowing for a more effective delivery of conventional therapeutics to the cancer cells; antibodies that activate a macrophage-mediated immune response to the tumor and overcome its immunosuppressive environment; and inhibitors of signaling pathways that promote the vascularization of the tumor.
Copyright © 2012, Transworld Research Network.