Molecular-targeted agents in pancreatic cancer.

Abstract

Despite the acceptance of gemcitabine as the standard first-line agent for the treatment of advanced pancreatic cancer as well as the improved response rates seen with gemcitabine combinations, novel therapies are needed for this disease, which has one of the lowest survival rates. The growing understanding of the molecular basis of pancreatic cancer and the recent introduction of targeted therapeutic agents have initiated novel studies that have the potential to improve on existing treatments. We review the rationale and the clinical studies of therapeutic agents that target some of the molecular abnormalities commonly found in pancreatic cancer. Matrix metalloproteinase inhibitors (MMPIs), farnesyltransferase inhibitors (FTIs), and tyrosine-kinase inhibitors and monoclonal antibodies against growth factors or their receptors are novel agents that have undergone phase II or III trials. Phase III studies of MMPIs, alone or in combination with gemcitabine, and phase III studies of FTIs have produced disappointing results. Other agents in earlier phases of clinical development remain promising. Despite the negative studies of MMPIs and FTIs, the results of phase II trials of other drugs are encouraging. Targeted agents may improve the prognosis of pancreatic cancer.