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

Chandhanayingyong C, Kim Y, Staples JR, Hahn C, Lee FY - Sarcoma (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus

MAPK/ERK signaling in osteosarcomas, Ewing sarcomas, and chondrosarcomas.
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Related In: Results  -  Collection


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fig2: MAPK/ERK signaling in osteosarcomas, Ewing sarcomas, and chondrosarcomas.

Mentions: There is a relative paucity of literature concerning the role of MAPK/ERK in bone sarcomas. Various viewpoints about the significance of MAPK/ERK demonstrate that this pathway's role in sarcoma is still being unraveled. It is known that osteosarcomas, Ewing sarcomas, and high-grade chondrosarcomas exhibit heightened pMAPK/pERK1/2 expression (Figure 2). Therefore, targeting MAPK/ERK1/2 could develop a modern molecular adjuvant therapy for bone sarcomas. To understand the therapeutic importance of RAF-MEK-ERK pathway targeting in bone sarcomas, it is necessary to update the results of experimental and clinical trial data.


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

Chandhanayingyong C, Kim Y, Staples JR, Hahn C, Lee FY - Sarcoma (2012)

MAPK/ERK signaling in osteosarcomas, Ewing sarcomas, and chondrosarcomas.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3345255&req=5

fig2: MAPK/ERK signaling in osteosarcomas, Ewing sarcomas, and chondrosarcomas.
Mentions: There is a relative paucity of literature concerning the role of MAPK/ERK in bone sarcomas. Various viewpoints about the significance of MAPK/ERK demonstrate that this pathway's role in sarcoma is still being unraveled. It is known that osteosarcomas, Ewing sarcomas, and high-grade chondrosarcomas exhibit heightened pMAPK/pERK1/2 expression (Figure 2). Therefore, targeting MAPK/ERK1/2 could develop a modern molecular adjuvant therapy for bone sarcomas. To understand the therapeutic importance of RAF-MEK-ERK pathway targeting in bone sarcomas, it is necessary to update the results of experimental and clinical trial data.

Bottom Line: 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.

View Article: PubMed Central - PubMed

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

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.

No MeSH data available.


Related in: MedlinePlus