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Hedgehog Signaling Inhibitors as Anti-Cancer Agents in Osteosarcoma

Laboratory for Orthopaedic Research, Balgrist University Hospital, Sarcoma Center-UZH University of Zurich, Zurich 8008, Switzerland
Author to whom correspondence should be addressed.
Academic Editor: Hui-Wen Lo
Cancers 2015, 7(2), 784-794;
Received: 7 April 2015 / Revised: 30 April 2015 / Accepted: 7 May 2015 / Published: 13 May 2015
PDF [381 KB, uploaded 13 May 2015]


Osteosarcoma is a rare type of cancer associated with a poor clinical outcome. Even though the pathologic characteristics of OS are well established, much remains to be understood, particularly at the molecular signaling level. The molecular mechanisms of osteosarcoma progression and metastases have not yet been fully elucidated and several evolutionary signaling pathways have been found to be linked with osteosarcoma pathogenesis, especially the hedgehog signaling (Hh) pathway. The present review will outline the importance and targeting the hedgehog signaling (Hh) pathway in osteosarcoma tumor biology. Available data also suggest that aberrant Hh signaling has pro-migratory effects and leads to the development of osteoblastic osteosarcoma. Activation of Hh signaling has been observed in osteosarcoma cell lines and also in primary human osteosarcoma specimens. Emerging data suggests that interference with Hh signal transduction by inhibitors may reduce osteosarcoma cell proliferation and tumor growth thereby preventing osteosarcomagenesis. From this perspective, we outline the current state of Hh pathway inhibitors in osteosarcoma. In summary, targeting Hh signaling by inhibitors promise to increase the efficacy of osteosarcoma treatment and improve patient outcome. View Full-Text
Keywords: osteosarcoma; hedgehog signaling; GLI; SMO; hedgehog inhibitors osteosarcoma; hedgehog signaling; GLI; SMO; hedgehog inhibitors

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kumar, R.M.R.; Fuchs, B. Hedgehog Signaling Inhibitors as Anti-Cancer Agents in Osteosarcoma. Cancers 2015, 7, 784-794.

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