Targeting the β-catenin/TCF transcriptional complex in the treatment of multiple myeloma

• DOI: 10.1073/pnas.0610299104
• Publication Date: 2007-04-24T15:46:17Z
• Authors: Kumar Sukhdeo; Mala Mani; Yunyu Zhang; Jui Dutta; Hiroshi Yasui; Melissa D. Rooney; Daniel E. Carrasco; Mei Zheng; Haiying He; Yu-Tzu Tai; Constantine Mitsi...; Kenneth C. Anderson; Daniel R. Carrasco
• Keywords: Beta-catenin; LRP6

Multiple myeloma (MM) is an invariably fatal form of cancer characterized by clonal proliferation malignant plasma cells in the bone marrow. The canonical Wnt signaling pathway activated MM through constitutively active beta-catenin, a messenger molecule relevant to growth, survival, and migration cells. identification number small molecular compounds, such as PKF115-584, which disrupt interaction transcriptionally beta-catenin/TCF protein complex, provides valuable new therapeutic tools target alternative independent proteasome. Here we evaluated transcriptional, proteomic, changes, biological sequelae associated with inhibition PKF115-584. compound blocks expression genes induces cytotoxicity both patient cell lines without significant effect normal In xenograft models human MM, PKF115-584 inhibits tumor growth prolongs survival. Taken together, these data demonstrate efficacy disrupting transcriptional complex exploit dependence on approach treatment MM.