替西罗莫司治疗新诊断的晚期头颈部鳞状细胞癌患者的药效学评价。
Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.
机构信息
Department of Otolaryngology-Head and Neck Surgery, Louisiana State University Health Sciences Center, Shreveport, LA, USA.
出版信息
Head Neck. 2010 Dec;32(12):1619-28. doi: 10.1002/hed.21374.
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.
背景
在头颈部鳞状细胞癌（HNSCC）的手术切缘中，哺乳动物雷帕霉素靶蛋白（mTOR）通路的激活是复发的预测因子，有微小残留病的患者可能受益于 mTOR 抑制剂替西罗莫司的辅助治疗。
方法
评估每周 3 次给予 25mg 替西罗莫司对 HNSCC 患者肿瘤和外周血单核细胞（PBMC）中 Akt/mTOR 通路生物标志物的影响。评估了不良反应。
结果
替西罗莫司显著降低了肿瘤中 pS6 和 p4E-BP1，以及 PBMC 中的 pS6 和 pAkt（p<.05）。肿瘤组织中 pAkt（Ser473）没有明显上调。副作用轻微且可逆。
结论
HNSCC 的肿瘤和 PBMC 中均观察到 mTOR 通路的显著抑制，且副作用极小。mTOR 抑制剂可能可作为微小残留病患者的辅助治疗，在此情况下 PBMC 是潜在的替代标志物。
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