Targeting insulin-like growth factor 1 receptor in sarcomas.
OBJECTIVE
The present review examines the rationale for targeting insulin-like growth factor-I receptor in sarcoma therapy and highlights some key issues that need to be addressed as clinical trials targeting insulin-like growth factor-I receptor proceed.


RESULTS
Preclinical evidence supports proof of principle for targeting insulin-like growth factor-I receptor signaling in sarcomas. The insulin-like growth factor system is activated by or associated with most of the fusion oncoproteins that genetically characterize a group of sarcomas, but alterations in this pathway appear as a common feature. Correlation of cancer risk with insulin-like growth factor-I receptor signaling expression and polymorphisms has also been described. Blockade of insulin-like growth factor-I receptor functions results in an inhibition of tumor growth and metastasis, both when the targeted drugs were used as single agents and in combined therapies. Antibodies against insulin-like growth factor-I receptor and small kinase inhibitors represent, at this point, the most probable clinical options.


CONCLUSIONS
Sarcomas are good candidates for the design of a clinical study targeting insulin-like growth factor-I receptor. An attention to schedule with chemotherapy agents and new drugs, measurement of relevant indicators of response and better molecular understanding of the metabolic functions of insulin-like growth factor-I receptor and its functional relationship with insulin receptor are necessary to proceed safely with the design of anti-insulin-like growth factor strategies.
Scotlandi
Katia
K
Laboratory of Oncologic Research, Istituti Ortopedici Rizzoli, Bologna, Italy. katia.scotlandi@ior.it
Picci
Piero
P
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1