title: Synergistic antiproliferative and antiangiogenic effects of EGFR and mTOR inhibitors.
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.
authors.affiliation: Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Viale O. Flacco, 65, 70124 Bari, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Porcelli
authors.forename: A E
authors.initials: AE
authors.lastname: Quatrale
authors.forename: P
authors.initials: P
authors.lastname: Mantuano
authors.forename: N
authors.initials: N
authors.lastname: Silvestris
authors.forename: J F
authors.initials: JF
authors.lastname: Rolland
authors.forename: L
authors.initials: L
authors.lastname: Biancolillo
authors.forename: A
authors.initials: A
authors.lastname: Paradiso
authors.forename: A
authors.initials: A
authors.lastname: Azzariti
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases