Review Article
MAPK/ERK Signaling in Osteosarcomas, Ewing Sarcomas and Chondrosarcomas: Therapeutic Implications and Future Directions
Table 1
Therapeutic implications of Ras-Raf-MEK-ERK targeting in bone sarcomas.
| Sarcoma types | Study design | Target | Inhibitor types | Results | References |
| | In vivo* | pERK1/2 | MEK inhibitor (PD98059) | Prolonged survival increase chemosensitivity | [24] | Osteosarcoma | In vivo* | pERK1/2 | RAF inhibitors (Sorafenib) | Growth inhibition | [36] | In vivo* | pERK1/2 | RAF inhibitors (Sorafenib) | Decrease lung metastasis antitumoral activity | [35] | | Clinical Trial (Phase II) () | pERK1/2 | RAF inhibitors (Sorafenib) | Clinical benefit (PR + MR + SD) >6 months = 29% | [37] | | In vivo* | pERK1/2 | RAF inhibitors (Sorafenib) | Growth inhibition | [36] | Ewing’s sarcoma | In vivo* | pERK1/2 PIP3K | U0126 LY294002 | Increase chemosensitivity | [38] | | Clinical trial (Phase I) () | pERK1/2 | RAF inhibitors (Sorafenib) | Not reported (ongoing) | [39] |
Chondrosarcoma | Clinical trial (Phase II) () | pERK1/2 | RAF inhibitors (Sorafenib) | Prolonged stable disease | [40] | Clinical trial (Phase II) () | pERK1/2 | RAF inhibitors (Sorafenib) | Prolonged stable disease for >6 months | [41] |
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PR: Partial response; MR: Minor response; SD: Stable disease, *Human sarcoma xenografts in mice.
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