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) (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.