The role of Wnt/β-catenin signaling pathway in the pathogenesis and treatment of multiple myeloma (review).

Multiple myeloma (MM) is a refractory hematological malignancy characterized by aberrant accumulation of plasma cells. Patients with MM are susceptible to becoming resistant to chemotherapy, eventually leading to relapse. Progression of MM is largely dependent on the bone marrow microenvironment. Stromal cells in the bone marrow microenvironment secrete Wnt ligands to activate Wnt signaling in MM, which is mediated through the transcription regulator β-catenin. In addition, Wnt/β-catenin pathway encourages osteoblast differentiation and bone formation, dysregulation of which is responsible for proliferation and drug resistance of MM cells. As a result, direct inhibition or silencing of β-catenin or associated genes in the Wnt/β-catenin pathway has been proposed to be an effective therapeutic anti-MM strategy. However, the underlying regulatory mechanism of the Wnt/β-catenin pathway in MM remains to be fully elucidated. Herein, we summarized research advances on the specific genes and molecular biology process of Wnt/β-catenin pathway involved in tumorigenesis of MM, as well as the interaction with bone marrow microenvironment. Additionally, comprehensive summaries of drugs or small molecule inhibitors acting on Wnt/β-catenin pathway and targeting MM were introduced. This review intends to provide an overview of theoretical supports for novel Wnt/β-catenin pathway based treatment strategies in MM.