1. Academic Validation
  2. WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

WNT signaling drives cholangiocarcinoma growth and can be pharmacologically inhibited

  • J Clin Invest. 2015 Mar 2;125(3):1269-85. doi: 10.1172/JCI76452.
Luke Boulter Rachel V Guest Timothy J Kendall David H Wilson Davina Wojtacha Andrew J Robson Rachel A Ridgway Kay Samuel Nico Van Rooijen Simon T Barry Stephen J Wigmore Owen J Sansom Stuart J Forbes
Abstract

Cholangiocarcinoma (CC) is typically diagnosed at an advanced stage and is refractory to surgical intervention and chemotherapy. Despite a global increase in the incidence of CC, little progress has been made toward the development of treatments for this Cancer. Here we utilized human tissue; CC cell xenografts; a p53-deficient transgenic mouse model; and a non-transgenic, chemically induced rat model of CC that accurately reflects both the inflammatory and regenerative background associated with human CC pathology. Using these systems, we determined that the Wnt pathway is highly activated in CCs and that inflammatory macrophages are required to establish this WNT-high state in vivo. Moreover, depletion of macrophages or inhibition of Wnt signaling with one of two small molecule Wnt inhibitors in mouse and rat CC models markedly reduced CC proliferation and increased Apoptosis, resulting in tumor regression. Together, these results demonstrate that enhanced Wnt signaling is a characteristic of CC and suggest that targeting Wnt signaling pathways has potential as a therapeutic strategy for CC.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117244
    99.45%, c-Fms Inhibitor