mTOR co-targeting strategies for head and neck cancer therapy.
mTOR co-targeting strategies for head and neck cancer therapy.
复制标题
头颈癌治疗的 mTOR 联合靶向策略
DOI：
10.1007/s10555-017-9688-7
复制
发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Gutkind JS
中科院分区：
文献类型：
--
作者：
Wang Z;Valera JC;Zhao X;Chen Q;Gutkind JS
头颈部鳞状细胞癌（HNSCC）是全球第六大最常见的恶性肿瘤。迫切需要开发有效的治疗方法来预防和治疗HNSCC。最近对HNSCC基因组景观的深度测序揭示了这种恶性肿瘤中遗传改变的多样性和多样性。尽管在每个肿瘤中发现了大量不同的特定分子，但它们都只参与少数驱动信号通路。其中，PI3K/mTOR通路是最常被激活的，它在癌症的发生和发展中起着核心作用。反过来，靶向mTOR可能代表了HNSCC的精确治疗方法。事实上，mTOR抑制在HNSCC实验系统中发挥了强大的抗肿瘤活性，mTOR靶向临床试验显示出令人鼓舞的结果。然而，晚期HNSCC患者可能表现出不可预测的耐药性，对其分子基础的分析表明，共同靶向策略可能提供更有效的选择。此外，尽管违反直觉，但新出现的证据表明，mTOR抑制可能增强抗肿瘤免疫反应。这些新发现提高了mTOR抑制剂和免疫肿瘤药物联合治疗HNSCC的可能性，可能为HNSCC提供新的精确治疗选择。
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression. In turn, targeting of mTOR may represent a precision therapeutic approach for HNSCC. Indeed, mTOR inhibition exerts potent anti-tumor activity in HNSCC experimental systems, and mTOR targeting clinical trials show encouraging results. However, advanced HNSCC patients may exhibit unpredictable drug resistance, and the analysis of its molecular basis suggests that co-targeting strategies may provide a more effective option. In addition, although counterintuitive, emerging evidence suggests that mTOR inhibition may enhance the anti-tumor immune response. These new findings raise the possibility that the combination of mTOR inhibitors and immune oncology agents may provide novel precision therapeutic options for HNSCC.
登录
查看更多内容
影响因子：
5.7
作者：
Ekshyyan O;Rong Y;Rong X;Pattani KM;Abreo F;Caldito G;Chang JK;Ampil F;Glass J;Nathan CO
通讯作者：
Nathan CO
影响因子：
3.3
作者：
Czeminski, Rakefet;Amornphimoltham, Panomwat;Gutkind, J. Silvio
通讯作者：
Gutkind, J. Silvio
影响因子：
--
作者：
Coppock JD;Vermeer PD;Vermeer DW;Lee KM;Miskimins WK;Spanos WC;Lee JH
通讯作者：
Lee JH
DOI：
10.1038/nri3198
发表时间：
2012-04-20
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
158.5
作者：
Bonner, JA;Harari, PM;Ang, KK
通讯作者：
Ang, KK