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Sarcoma
Volume 2012, Article ID 404810, 8 pages
http://dx.doi.org/10.1155/2012/404810
Review Article

MAPK/ERK Signaling in Osteosarcomas, Ewing Sarcomas and Chondrosarcomas: Therapeutic Implications and Future Directions

1Center for Orthopedic Research (COR), Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA
2Department of Orthopedic Surgery, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand

Received 8 December 2011; Accepted 9 January 2012

Academic Editor: Charles Scoggins

Copyright © 2012 Chandhanarat Chandhanayingyong et al. 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.

Abstract

The introduction of cytotoxic chemotherapeutic drugs in the 1970’s improved the survival rate of patients with bone sarcomas and allowed limb salvage surgeries. However, since the turn of the century, survival data has plateaued for a subset of metastatic, nonresponding osteo, and/or Ewing sarcomas. In addition, most high-grade chondrosarcoma does not respond to current chemotherapy. With an increased understanding of molecular pathways governing oncogenesis, modern targeted therapy regimens may enhance the efficacy of current therapeutic modalities. Mitogen-Activated Protein Kinases (MAPK)/Extracellular-Signal-Regulated Kinases (ERK) are key regulators of oncogenic phenotypes such as proliferation, invasion, angiogenesis, and inflammatory responses; which are the hallmarks of cancer. Consequently, MAPK/ERK inhibitors have emerged as promising therapeutic targets for certain types of cancers, but there have been sparse reports in bone sarcomas. Scattered papers suggest that MAPK targeting inhibits proliferation, local invasiveness, metastasis, and drug resistance in bone sarcomas. A recent clinical trial showed some clinical benefits in patients with unresectable or metastatic osteosarcomas following MAPK/ERK targeting therapy. Despite in vitro proof of therapeutic concept, there are no sufficient in vivo or clinical data available for Ewing sarcomas or chondrosarcomas. Further experimental and clinical trials are awaited in order to bring MAPK targeting into a clinical arena.