Cancers, Vol. 16, Pages 1050: Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts

Cancers, Vol. 16, Pages 1050: Combined Antitumor Effect of the Serine Protease Urokinase Inhibitor Upamostat and the Sphingosine Kinase 2 Inhibitor Opaganib on Cholangiocarcinoma Patient-Derived Xenografts Cancers doi: 10.3390/cancers16051050 Authors: Faizal Z. Asumda Nellie A. Campbell Mohamed A. Hassan Reza Fathi Daniella F. Vasquez Rico Melanie Kiem Ethan V. Vang Yo Han Kim Xin Luo Daniel R. O’Brien Sarah A. Buhrow Joel M. Reid Michael J. Moore Vered Katz Ben-Yair Mark L. Levitt Jennifer L. Leiting Amro M. Abdelrahman Xinli Zhu Fabrice Lucien Mark J. Truty Lewis R. Roberts Upamostat is an orally available small-molecule serine protease inhibitor that is a highly potent inhibitor of trypsin 1, trypsin 2, trypsin 3 (PRSS1/2/3), and the urokinase-type plasminogen activator (uPA). These enzymes are expressed in many cancers, especially during tissue remodeling and subsequent tumor cell invasion. Opaganib (ABC294640), a novel, orally available small molecule is a selective inhibitor of the phosphorylation of sphingosine to sphingosine-1-phosphate (S-1-P) by sphingosine kinase 2 (SPHK2). Both sphingosine kinase 1 (SPHK1) and SPHK2 are known to regulate the proliferation-inducing compound S-1-P. However, SPHK2 is more critical in cancer pathogenesis. The goal of this project was to investigate the potential antitumor effects of upamostat and opaganib, individually and in combination, on cholangiocarcinoma (CCA) xenografts in nude ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research