Molecular targeted therapies in pancreatic cancer

Pancreatic cancer, one of the deadliest malignancies, is a complex disease consisting of heterogeneous cancer cells with deregulated signaling pathways and a myriad of microenvironment cells, including infiltrating immune cells and fibroblasts, that impact tumor growth and susceptibility to conventional chemotherapy. Understanding the signaling pathways that drive pancreatic cancer is crucial to the development of novel targeted therapies to combat the disease, which is largely refractory to conventional therapeutic options. Among these pathways are the Hedgehog, NOTCH, Wnt, MET, and TGF-β pathways that control not only bulk tumor growth, but also self-renewal of cancer stem cells and maintenance of the desmoplastic stroma characteristic of the disease. In addition to altered signaling pathways, many cells within the tumor microenvironment promote both tumor growth and serve as a barrier to chemotherapy. Here we will discuss how targeting these components of the disease may increase the efficacy with which it is treated.