Wnt Signaling in Ewing Sarcoma, Osteosarcoma, and Malignant Peripheral Nerve Sheath Tumors
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Purpose of Review
Wnt signaling plays a central role in development and homeostasis, and its dysregulation is a common event in many types of human cancer. Here we explore in detail the contributions of Wnt signaling to the initiation and maintenance of three types of saroma: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors. This review provides an overview of the Wnt signaling pathway and explores in detail the current knowledge about its role in the initiation or maintenance of three tumor types: Ewing sarcoma, osteosarcoma, and malignant peripheral nerve sheath tumors.
Recent work has assessed the role(s) of Wnt signaling within these cell types. This review provides an overview of the mechanistic insights that have been gained from a number of recent studies to set the foundation for potential therapeutic applications.
Wnt signaling has emerged as a potentially critical pathway in maintaining the growth of these types of tumors. Given the fact that many new inhibitors of the pathway have recently or will soon enter Phase 1 clinical trials, it is likely that assessment of their activity in these tumor types will occur in human patients.
KeywordsWnt β-catenin Ewing sarcoma Neurofibromatosis Type 1 Osteosarcoma Malignant peripheral nerve sheath tumors
Work in these areas is supported by NIH grants to BOW (AR053293) and PJG (CA188314). MRS is supported by the Francis S. Collins Scholars Program in Neurofibromatosis Clinical and Translational Research sponsored by Johns Hopkins University’s Neurofibromatosis Therapeutic Acceleration Program (NTAP). PJG has received additional support from Alex’s Lemonade Stand Reach Award and Lily’s Garden Foundation. We thank Nicole Ethen for assistance with preparation of the figure.
Compliance with Ethical Standards
Conflict of Interest
Matthew Pridgeon, Patrick Grohar, and Matthew Steensma declare no conflict of interest.
Bart Williams reports speaker honoraria from Vertex Pharmaceuticals and personal fees as a member of the board of scientific advisor from Surrozen.
Human and Animal Rights and Informed Consent
This article does not contain any studies that include human or animal subjects performed by any of the authors.
BOW has received honoraria from Amgen and Vertex Pharmaceuticals. BOW serves on the Board of Scientific Advisors for, and owns stock inSurrozen.
Papers of particular interest, published recently, have been highlighted as: •• Of major importance
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