Approach to treat bone loss might increase bone cancer risk

One approach being considered as a new way to treat osteoporosis is the development of molecules that block the action of proteins that inhibit the Wnt signaling pathway. However, dysregulated Wnt signaling is associated with several cancers. Further, David Thomas and colleagues, at Peter MacCallum Cancer Centre, Australia, have now shown that the gene responsible for making the Wnt signaling pathway inhibitor WIF1 is silenced in human osteosarcomas (the most common form of bone cancer) and that its absence in mice accelerated the development of radiation-induced osteosarcomas. The authors therefore conclude that targeting Wnt signaling pathway inhibitors is likely to increase susceptibility to osteosarcomas. Thus, both the authors and, in an accompany commentary, Greg Enders, at Fox Chase Cancer Center, Philadelphia, note that caution is needed before this approach is used in clinical trials to treat patients with bone loss disorders such as osteoporosis.

TITLE: Wnt inhibitory factor 1 is epigenetically silenced in human osteosarcoma, and targeted disruption accelerates osteosarcomagenesis in mice

AUTHOR CONTACT:
David M. Thomas
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Phone: 613-9656-1111; Fax: 613-9656-1411; E-mail: david.thomas@petermac.org.

View the PDF of this article at: https://www.the-jci.org/article.php?id=37175

ACCOMPANYING COMMENTARY
TITLE: Wnt therapy for bone loss: golden goose or Trojan horse?

AUTHOR CONTACT:
Greg H. Enders
Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA.
Phone: (215) 214-3956; Fax: (215) 728-4333; E-mail: Greg.Enders@fccc.edu.

View the PDF of this article at: https://www.the-jci.org/article.php?id=38973