Challenges in developing targeted therapy for pancreatic adenocarcinoma

Background: Pancreatic adenocarcinoma is a leading cause of cancer deaths in the US. Gemcitabine-based chemotherapy remains the cornerstone treatment for advanced pancreatic cancers. Research into the molecular pathogenesis of pancreatic cancers has allowed scientists to understand the complex heterogeneous signals associated with them. Targeting these pathways with chemical inhibitors could improve patient outcome. Objective: To describe the molecular heterogeneity typical of pancreatic cancers and to discuss targeted therapies in development, and the challenges facing these agents. Methods: We reviewed Pub Med. literature, clinical trial database (clinicaltrials.gov), American Society of Clinical Oncology (ASCO) and American Association of Cancer Research (AACR) websites. Conclusions: Molecular pathogenesis of pancreatic cancer involves multiple pathways and defined mutations. This molecular heterogeneity is a major reason for failure of targeted therapy. Targeting multiple oncogenic pathways using novel targeted therapies could improve patient survival.