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) (N = 35) | 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) (N = 34) | pERK1/2 | RAF inhibitors (Sorafenib) | Not reported (ongoing) | [39] | |
| Chondrosarcoma | Clinical trial (Phase II) (N = 26) | pERK1/2 | RAF inhibitors (Sorafenib) | Prolonged stable disease | [40] |
| Clinical trial (Phase II) (N = 147) | pERK1/2 | RAF inhibitors (Sorafenib) | Prolonged stable disease for >6 months | [41] |
PR: Partial response; MR: Minor response; SD: Stable disease, *Human sarcoma xenografts in mice.