Current and evolving therapies for metastatic pancreatic cancer: Are we stuck with cytotoxic chemotherapy?

At present, front-line therapy for metastatic pancreatic ductal adenocarcinoma is combination chemotherapy, most commonly FOLFIRINOX (fluorouracil, irinotecan, and oxaliplatin) or gemcitabine and nanoparticle albumin-bound paclitaxel. Despite a better understanding of the genomic landscape and the importance of the tumor microenvironment, we have not made a seismic shift in the overall survival for this disease. Given our growing understanding of the biology of pancreatic ductal adenocarcinoma, the question remains whether novel, noncytotoxic agents will augment or even replace conventional chemotherapy. The thrust of ongoing efforts can be divided into broad categories, including exploiting the DNA damage repair phenotype, stroma and specific pathway-targeting agents, and enhancing immune destruction of pancreatic ductal adenocarcinoma. In this article, we review the current and evolving therapeutic landscape of metastatic pancreatic cancer.