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

Chandhanarat Chandhanayingyong1, Yuhree Kim, J Robert Staples

  • 1Center for Orthopedic Research (COR), Department of Orthopedic Surgery, Columbia University, New York, NY 10032, USA.

Sarcoma
|May 12, 2012
PubMed

Insights

Targeting Mitogen-Activated Protein Kinases (MAPK)/Extracellular-Signal-Regulated Kinases (ERK) shows promise for treating bone sarcomas like osteosarcoma, Ewing sarcoma, and chondrosarcoma, though more clinical trials are needed.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Cytotoxic chemotherapy improved survival for bone sarcomas but has plateaued for metastatic osteosarcomas and Ewing sarcomas.
  • High-grade chondrosarcoma remains largely unresponsive to current chemotherapy regimens.
  • Understanding oncogenic molecular pathways offers opportunities for targeted therapy.

Purpose of the Study:

  • To explore the potential of Mitogen-Activated Protein Kinases (MAPK)/Extracellular-Signal-Regulated Kinases (ERK) pathway inhibitors as targeted therapies for bone sarcomas.
  • To review the current evidence for MAPK/ERK targeting in osteosarcoma, Ewing sarcoma, and chondrosarcoma.
  • To identify gaps in research and clinical application for MAPK/ERK inhibitors in bone sarcomas.

Main Methods:

  • Review of existing literature on MAPK/ERK signaling in cancer.
  • Analysis of preclinical and clinical data regarding MAPK/ERK inhibitors in bone sarcomas.
  • Evaluation of in vitro, in vivo, and clinical trial results.

Main Results:

  • MAPK/ERK signaling is implicated in key oncogenic phenotypes, including proliferation and invasion in bone sarcomas.
  • Preclinical studies suggest MAPK targeting inhibits proliferation, invasion, metastasis, and drug resistance in bone sarcomas.
  • A recent clinical trial indicated some benefit of MAPK/ERK targeting in unresectable or metastatic osteosarcomas.

Conclusions:

  • MAPK/ERK inhibitors represent a promising therapeutic strategy for bone sarcomas, particularly osteosarcoma.
  • Sufficient in vivo and clinical data are lacking for Ewing sarcomas and chondrosarcomas.
  • Further experimental and clinical trials are essential to establish MAPK/ERK targeting in the clinical treatment of bone sarcomas.

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