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

Autor: Cody Hahn, Francis Y. Lee, Chandhanarat Chandhanayingyong, J. Robert Staples, Yuhree Kim
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Zdroj: Sarcoma, Vol 2012 (2012)
Sarcoma
ISSN: 1369-1643
Popis: 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. Despitein vitroproof of therapeutic concept, there are no sufficientin vivoor 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.
Databáze: OpenAIRE
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