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Combining molecular targeted agents with radiation therapy for malignant gliomas

Authors Scaringi C, Enrici RM, Minniti G

Received 14 May 2013

Accepted for publication 28 June 2013

Published 9 August 2013 Volume 2013:6 Pages 1079—1095


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Claudia Scaringi,1 Riccardo Maurizi Enrici,1 Giuseppe Minniti1,2

1Department of Radiation Oncology, Sant'Andrea Hospital, University Sapienza, Rome, Italy; 2Department of Neuroscience, Neuromed Institute, Pozzilli, Italy

Abstract: The expansion in understanding the molecular biology that characterizes cancer cells has led to the rapid development of new agents to target important molecular pathways associated with aberrant activation or suppression of cellular signal transduction pathways involved in gliomagenesis, including epidermal growth factor receptor, vascular endothelial growth factor receptor, mammalian target of rapamycin, and integrins signaling pathways. The use of antiangiogenic agent bevacizumab, epidermal growth factor receptor tyrosine kinase inhibitors gefitinib and erlotinib, mammalian target of rapamycin inhibitors temsirolimus and everolimus, and integrin inhibitor cilengitide, in combination with radiation therapy, has been supported by encouraging preclinical data, resulting in a rapid translation into clinical trials. Currently, the majority of published clinical studies on the use of these agents in combination with radiation and cytotoxic therapies have shown only modest survival benefits at best. Tumor heterogeneity and genetic instability may, at least in part, explain the poor results observed with a single-target approach. Much remains to be learned regarding the optimal combination of targeted agents with conventional chemoradiation, including the use of multipathways-targeted therapies, the selection of patients who may benefit from combined treatments based on molecular biomarkers, and the verification of effective blockade of signaling pathways.

Keywords: glioblastoma, high-grade glioma, targeted therapy, radiation therapy, temozolomide

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