title: Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.
abstract: BACKGROUND
  Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor.
  
  
  METHODS
  The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed.
  
  
  RESULTS
  Temsirolimus significantly decreased pS6 and p4E-BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser(473)) in tumor tissue. Side effects were minimal and reversible.
  
  
  CONCLUSIONS
  Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
authors.forename: Oleksandr
authors.initials: O
authors.lastname: Ekshyyan
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Mills
authors.forename: Timothy
authors.initials: T
authors.lastname: Lian
authors.forename: Nazanin
authors.initials: N
authors.lastname: Amirghahari
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Rong
authors.forename: Mary
authors.initials: M
authors.lastname: Lowery-Nordberg
authors.forename: Fleurette
authors.initials: F
authors.lastname: Abreo
authors.forename: Diana M
authors.initials: DM
authors.lastname: Veillon
authors.forename: Gloria
authors.initials: G
authors.lastname: Caldito
authors.forename: Lisa
authors.initials: L
authors.lastname: Speicher
authors.forename: Jonathan
authors.initials: J
authors.lastname: Glass
authors.forename: Cherie-Ann O
authors.initials: CO
authors.lastname: Nathan
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus