PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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.
PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: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.
Authors: Erin R King; Zhifei Zu; Yvonne T M Tsang; Michael T Deavers; Anais Malpica; Samuel C Mok; David M Gershenson; Kwong-Kwok Wong Journal: Gynecol Oncol Date: 2011-07-02 Impact factor: 5.482
Authors: Martin G Belinsky; Lori Rink; Kathy Q Cai; Michael F Ochs; Burton Eisenberg; Min Huang; Margaret von Mehren; Andrew K Godwin Journal: Cell Cycle Date: 2008-10-07 Impact factor: 4.534