title: Indications for an alternative effective treatment of head and neck squamous cell carcinoma with temsirolimus plus bevacizumab:  from bench to bedside?
abstract: Head and neck squamous cell carcinoma (HNSCC) is a group of tumors known to be sensitive to chemotherapy and radiotherapy in patients who are treatment naive. However, when recurrences do occur, these tumors generally become resistant and objective responses to therapy at that point tend to be less effective. There has been an increasing interest in developing novel molecular-targeted agents that specifically modulate growth factor and signaling pathways that are unregulated in HNSCC tumor cells. Combinations of vascular endothelial growth factor and mammalian target of rapamycin inhibitors have been used in some types of neoplasms, but no such efforts have been made in HNSCC. In this study, we investigated the in vitro, in vivo, and clinical effects of the temsirolimus (mammalian target of rapamycin inhibitor, Tem) and bevacizumab (antivascular endothelial growth factor antibody, Bev) combination. In-vitro studies were carried out on the A431 human squamous epidermoid carcinoma cell line and in-vivo studies were carried out on A431 tumor cells implanted on female Nu/Nu*nuBR (athymic nude) mice. Also, the effectiveness of the Tem and Bev combination was tested clinically in two separate clinical cases of chemoresistant HNSCC. The in-vitro, in-vivo, and clinical results showed that this combination can be significantly effective. In conclusion, we discuss the theoretical basis of the molecular pharmacological interactions between Bev and Tem that could explain these good results. If the therapeutic index is ultimately well determined, the antitumor effect of Bev and Tem is very likely to yield fruitful results.
authors.affiliation: Department of Pharmacology, Medical School, University of Athens, Greece. dtrafal@med.uoa.gr
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Trafalis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Alifieris
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Dalezis
authors.forename: George
authors.initials: G
authors.lastname: Geromichalos
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Sitaras
mesh_terms: D000818:Animals; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; C401859:temsirolimus; D020123:Sirolimus