Targeting interleukin-6 as a treatment approach for peritoneal carcinomatosis
Neda Dadgar, Christopher Sherry, Jenna Zimmerman, Hyun Park, Catherine Lewis, Albert D. Donnenberg, Ali H. Zaidi, Yong Fan, Kunhong Xiao, David L. Bartlett, Vera S. Donnenberg, Patrick Wagner
Abstract
Peritoneal carcinomatosis (PC) is a complex manifestation of abdominal cancers, with a poor prognosis and limited treatment options. Recent work identifying high concentrations of the cytokine interleukin-6 (IL-6) and its soluble receptor (sIL-6-Rα) in the peritoneal cavity of patients with PC has highlighted this pathway as an emerging potential therapeutic target. This review article provides a comprehensive overview of the current understanding of the potential role of IL-6 in the development and progression of PC. We discuss mechansims by which the IL-6 pathway may contribute to peritoneal tumor dissemination, mesothelial adhesion and invasion, stromal invasion and proliferation, and immune response modulation. Finally, we review the prospects for targeting the IL-6 pathway in the treatment of PC, focusing on common sites of origin, including ovarian, gastric, pancreatic, colorectal and appendiceal cancer, and mesothelioma.