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. CONCLUSION: 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.
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. CONCLUSION: 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: Alfredo A Molinolo; Christina Marsh; Mohamed El Dinali; Nitin Gangane; Kaitlin Jennison; Stephen Hewitt; Vyomesh Patel; Tanguy Y Seiwert; J Silvio Gutkind Journal: Clin Cancer Res Date: 2012-03-12 Impact factor: 12.531
Authors: Vyomesh Patel; Christina A Marsh; Robert T Dorsam; Constantinos M Mikelis; Andrius Masedunskas; Panomwat Amornphimoltham; Cherie-Ann O Nathan; Cherie Ann Nathan; Bhuvanesh Singh; Roberto Weigert; Alfredo A Molinolo; J Silvio Gutkind Journal: Cancer Res Date: 2011-10-05 Impact factor: 12.701
Authors: Amanda Herzog; Yansong Bian; Robert Vander Broek; Bradford Hall; Jamie Coupar; Hui Cheng; Anastasia L Sowers; John D Cook; James B Mitchell; Zhong Chen; Ashok B Kulkarni; Carter Van Waes Journal: Clin Cancer Res Date: 2013-05-02 Impact factor: 12.531
Authors: Ryan J Brisson; Sara Kochanny; Saba Arshad; Allison Dekker; Jonas A DeSouza; Vassiliki Saloura; Everett E Vokes; Tanguy Y Seiwert Journal: Head Neck Date: 2019-09-04 Impact factor: 3.821