Abstract
Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in cancer treatment. In this regard, the EGFR and mTOR inhibitors have been used together to generate a synergistic effect and maximize the efficacy of each individual agent. Overall, the in vivo and in vitro evidences support the utilization of combinations targeting EGFR and mTOR, for malignancies characterized by deregulated EGFR/PI3K/Akt/ mTOR signalling cascade; whereas the clinical experience points out that the assessment of the therapeutic value of such combination awaits further investigations.
Keywords: EGFR, mTOR, combination therapy, biomarkers, clinical trials, single-agent therapy, targeted agents, tumor growth control, cancer, signalling cascade
Current Pharmaceutical Design
Title:Synergistic Antiproliferative and Antiangiogenic Effects of EGFR and mTOR Inhibitors
Volume: 19 Issue: 5
Author(s): L. Porcelli, A.E. Quatrale, P. Mantuano, N. Silvestris, J.F. Rolland, L. Biancolillo, A. Paradiso and A. Azzariti
Affiliation:
Keywords: EGFR, mTOR, combination therapy, biomarkers, clinical trials, single-agent therapy, targeted agents, tumor growth control, cancer, signalling cascade
Abstract: Single-agent therapy with molecularly targeted agents has shown limited success in tumor growth control, mainly because escape or resistance mechanisms are activated once a signalling molecule is inhibited. Rational combinations of target-specific agents could counteract this response providing a useful strategy in cancer treatment. In this regard, the EGFR and mTOR inhibitors have been used together to generate a synergistic effect and maximize the efficacy of each individual agent. Overall, the in vivo and in vitro evidences support the utilization of combinations targeting EGFR and mTOR, for malignancies characterized by deregulated EGFR/PI3K/Akt/ mTOR signalling cascade; whereas the clinical experience points out that the assessment of the therapeutic value of such combination awaits further investigations.
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Porcelli L., Quatrale A.E., Mantuano P., Silvestris N., Rolland J.F., Biancolillo L., Paradiso A. and Azzariti A., Synergistic Antiproliferative and Antiangiogenic Effects of EGFR and mTOR Inhibitors, Current Pharmaceutical Design 2013; 19 (5) . https://dx.doi.org/10.2174/1381612811306050918
DOI https://dx.doi.org/10.2174/1381612811306050918 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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