Sarcoma

Review Article

Targeted Therapies in Sarcomas: Challenging the Challenge

Table 1

Targets, drugs, and clinical trials. Drugs and their specific targets in sarcoma treatment and clinical trials with their results: positive (+), negative (−), or not published (x).


	Target	Drug	Clinical trial

Vascular endothelial growth factor	Tyrosine kinase inhibitors	Sunitinib	+	Phase II trial: non:GIST sarcoma [18].
			+	Phase II trial: leiomyosarcoma, liposarcoma, and malignant fibrous histiocytoma. [19].
			−	Phase II study: treatment of recurrent/persistent uterine leiomyosarcoma [20].
		Sorafenib	+	Phase II trial: patients with metastatic or recurrent sarcomas [28].
			+	Phase II trial: efficacy of sorafenib in STS [31].
			+	Phase II trial: relapsed and unresectable high-grade osteosarcoma [29].
			+	Phase II trial: advanced vascular sarcoma, high grade liposarcoma and leiomyosarcoma [30].
		Pazopanib	+	Phase II trial: patients with relapsed or refractory advanced STS [32].
			+	Phase III trial: placebo-controlled randomized trial in advanced STS [33].
		Dasatinib	x	No results published.
	Anti-VEGF antibodies	Bevacizumab	+	Phase II trial: doxorubicin and bevacizumab in patients with metastatic STS [43].
			+	Phase IB trial: efficacy of bevacizumab in combination with other drugs [44].

Insulin-like growth factor	Tyrosine kinase inhibitors	Clinical development	x	No results published.
	Anti-IGFR1 antibodies	AMG 479	+	Phase I trial: response of sarcoma patients to a fully monoclonal antibody to IGFR-1 [68].
		Figitumumab	−	Phase I trial: different sarcoma patients [70].
		IMC-A12 (cixutumumab)	+	Phase II trial: patients with advanced or metastatic STS and Ewing Sarcoma [91].

Mammalian target of rapamycin	mTORC1 tyrosine kinase inhibitors	Sirolimus	−	Phase II trial: combination with cyclophosphamide in sarcomas [91].
		Temsirolimus	+	Phase II trial: temsirolimus in pediatric patients with neuroblastoma, high-grade glioma, and rhabdomyosarcoma [95].
			−	Phase II trial: treatment in STS patients [94]
			+	Phase II trial: everolimus in STS or bone sarcoma [97]
		Everolimus	+	Phase II trial: treatment in patients with advanced bone and soft tissue sarcomas [99].
		Ridaforolimus	+	Phase III trial: placebo-controlled randomized sarcoma patient [99].

Hepatocyte growth factor receptor	MET inhibitors	ARQ197	+	Phase II trial: patients with microph thalmia transcription-family-(MiT-) associated tumors [107].
Virus	Tumor cell	Oncolytic poxvirus	+	Phase I trial: oncolytic poxvirus in different cancer patients [109].
Insulin-like growth factor/ mammalian target of rapamycin	Tyrosine kinase inhibitors	Figitumumab/ everolimus	+	Phase I trial: advanced sarcoma patients and other solid tumors [114].
Insulin-like growth factor/ mammalian target of rapamycin	Tyrosine kinase inhibitors	Cixutumumab/ temsirolimus	+	Phase I trial: patients with advanced cancer including sarcomas [115].

Other targets	ALK inhibitors	Crizotinib	+	Phase I trial: inflammatory myofibroblastic tumor with ALK overexpression [116].
	HDAC inhibitors		+	Ongoing clinical trials.
	PI3K/mTOR	NVP-BEZ235	+	Ongoing clinical trials.