Monoclonal antibodies and other targeted therapies for pancreatic cancer

Pancreatic cancer continues to be a challenging disease to treat because of its aggressive nature, advanced stage at the time of diagnosis, and limited treatment options that are available. Traditional cytotoxic chemotherapy provides modest benefit to patients with pancreatic adenocarcinoma. Recently, a FOLFIRINOX regimen revealed improved response in overall and progression-free survival over single-agent gemcitabine in metastatic pancreatic cancer, but there is still much needed advancement in the systemic treatment of pancreatic cancer. There is a growing interest in the development of novel agents, while our understanding of molecular pathogenesis of pancreatic adenocarcinoma continues to expand. With identification of various molecular pathways in pancreatic cancer tumorigenesis, potential targets for drug development have been pursued with the use of monoclonal antibodies and small-molecule inhibitors. Although preclinical studies with multiple targeted therapies demonstrated encouraging results in pancreatic cancer, only erlotinib, an epidermal growth factor receptor inhibitor, showed a marginal survival benefit in a phase III clinical trial, when combined with gemcitabine. As further signaling pathways and their importance in pancreatic cancer tumorigenesis are better understood, further clinical trials will need to be designed to study these targeted agents as single agents, in combination with other novel agents or in combination with cytotoxic chemotherapy. In this review, we present the current knowledge on targeted therapy in pancreatic adenocarcinoma and its application in clinical practice.