Journal
CURRENT OPINION IN ONCOLOGY
Volume 20, Issue 4, Pages 419-427Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CCO.0b013e328302edab
Keywords
biomarkers; insulin-like growth factor-1 receptor; metabolism; sarcomas; targeted therapies
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Purpose of review The present review examines the rationale for targeting insulin-like growth factor-1 receptor in sarcoma therapy and highlights some key issues that need to be addressed as clinical trials targeting insulin-like growth factor-1 receptor proceed. Recent findings Preclinical evidence supports proof of principle for targeting insulin-like growth factor-1 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-1 receptor signaling expression and polymorphisms has also been described. Blockade of insulin-like growth factor-1 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-1 receptor and small kinase inhibitors represent, at this point, the most probable clinical options. Summary Sarcomas are good candidates for the design of a clinical study targeting insulin-like growth factor-1 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 facto-1 receptor and its functional relationship with insulin receptor are necessary to proceed safely with the design of anti-insulin-like growth factor strategies.
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