Progress in the treatment of metastatic pancreatic cancer and the search for next opportunities.

A growing number of therapeutic options are now available for patients with metastatic pancreatic cancer, informed by positive results from recently completed phase III clinical trials. These have led to modest, if not necessarily transformative, improvements in clinical outcomes. Although the standard of care for metastatic disease remains cytotoxic therapy, a variety of novel therapeutic approaches are currently under active investigation, several of which have already demonstrated encouraging results in phase I/II studies. The following three broad categories (with significant overlap among them) are highlighted here: stromal-depleting agents, immunotherapies, and signal transduction inhibitors. The mechanistic rationale, limitations, and promise of each of these strategies specific to pancreatic cancer are discussed, as are the aspects of this disease and this patient population that pose ongoing challenges in terms of both therapeutic management and biomarker-driven trial design.