Abstract B28: Novel combination treatment designed to target both metastatic cells and proliferation in pancreatic ductal adenocarcinoma

Pancreatic cancer is the 4th most common cause of cancer-related deaths in the United States, with only a 7-9% 5-year survival rate. While there are a few combination treatments that have been shown to increase overall survival by several months, gemcitabine monotherapy, which has been used to treat PDAC since 2006, is still the most commonly administered first-line treatment. Our objective is to improve patient survival by providing a novel combination therapy designed to inhibit the growth of solid tumors and prevent metastatic cancer cells from reaching secondary organs. Our lab has recently shown that secreted interleukin 6 (IL-6) and interleukin 8 (IL-8) can induce a migratory phenotype in tumorigenic, metastatic cancer cells in triple-negative breast cancer models. Cells exposed to these cytokines display enhanced invasion through stromal environments, and this phenotype can be reversed by blocking the IL-6 and IL-8 receptors with the combined treatment of tocilizumab and reparixin. We hypothesized that this simultaneous blocking of IL-6 and IL-8 receptors would improve PDAC patient outcomes when used in combination with gemcitabine by targeting both proliferation and metastasis. Preliminary results show that this combination treatment has a positive effect in in vivo PDAC models. Our novel treatment combination was able to significantly reduce the tumor size, exceeding that seen from gemcitabine monotherapy. In addition, the triple combination reduced the metastatic burden and normalized the effect of the treatment among the mice in the group. Citation Format: Michelle Karl, Gabriella Russo, Bartholomew Starich, Haotian Tan, Denis Wirtz. Novel combination treatment designed to target both metastatic cells and proliferation in pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B28.