Overview of current and future biologically based targeted therapies in head and neck squamous cell carcinoma.
Overview of current and future biologically based targeted therapies in head and neck squamous cell carcinoma.
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DOI：
10.1186/1758-3284-1-6
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发表时间：
2009-03-02
期刊：
影响因子：
--
通讯作者：
Ralhan R
中科院分区：
文献类型：
--
作者：
Matta A;Ralhan R
基因组学、蛋白质组学、生物信息学和系统生物学的最新进展揭示了癌症中复杂的异常信号网络。积累的知识大大增加了发现药物开发的新分子靶点的机会。重点是设计针对多种信号通路的新治疗策略，以实现更有效的疾病管理。然而，将体外研究结果转化为患者管理往往面临重大挑战，限制了其临床疗效。在这里，我们将讨论如何理解失调的信号网络可以解释将实验室发现从实验室到临床的陷阱，并提出以头颈癌为原型克服这些问题的新方法。尽管包括手术、放疗和化疗在内的多模式治疗取得了进展，但HNSCC患者的5年生存率（5年生存率约为50%）并没有显著提高。单独使用EGFR和VEGF抑制剂的分子靶向治疗，或与常规治疗联合使用，都显示出有限的疗效改善。头颈部鳞状细胞癌（HNSCC）的关键信号通路失调包括EGFR、Ras、TGFβ、NFκB、Stat、Wnt/β-catenin和PI3-K/AKT/mTOR。这些相互关联的信号通路的异常活动有助于HNSCC的发展。深入了解这些通路和网络之间的相互作用将为开发针对多种分子成分的新策略奠定基础，从而更有效地预防和治疗HNSCC。
Recent advances in genomics, proteomics, bioinformatics and systems biology have unraveled the complex aberrant signaling networks in cancer. The knowledge accrued has dramatically increased the opportunities for discovery of novel molecular targets for drug development. Major emphasis is being laid on designing new therapeutic strategies targeting multiple signaling pathways for more effective disease management. However, the translation of in vitro findings to patient management often poses major challenges that limit their clinical efficacy. Here we will discuss how understanding the dysregulated signaling networks can explain the pitfalls in translating the laboratory findings from the bench-to-bedside and suggest novel approaches to overcome these problems using head and neck cancer as a prototype. The five year survival rates of HNSCC patients (about 50% at 5 years) have not improved significantly despite advancements in multimodality therapy including surgery, radiation and chemotherapy. Molecular targeted therapies with inhibitors of EGFR and VEGF either alone, or in combination with conventional treatments have shown limited improved efficacy. The key deregulated signaling pathways in head and neck squamous cell carcinoma (HNSCC) include EGFR, Ras, TGFβ, NFκB, Stat, Wnt/β-catenin and PI3-K/AKT/mTOR. The aberrant activities of these interrelated signaling pathways contribute to HNSCC development. In depth understanding of the cross-talks between these pathways and networks will form the basis of developing novel strategies for targeting multiple molecular components for more effective prevention and treatment of HNSCC.
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在未分离的局部晚期鳞状细胞癌中，对超分配和加速放疗以及联合化疗和放射治疗方案的荟萃分析。
影响因子：
3.8
作者：
Budach, W;Hehr, T;Budach, V;Belka, C;Dietz, K
通讯作者：
Dietz, K
影响因子：
5.7
作者：
Gillenwater, Ann M.;Zhong, Meiling;Lotan, Reuben
通讯作者：
Lotan, Reuben
影响因子：
11.5
作者：
Erjala, Kaisa;Sundvall, Maria;Elenius, Klaus
通讯作者：
Elenius, Klaus
影响因子：
45.3
作者：
Bourhis, Jean;Rivera, Fernando;Harstrick, Andreas
通讯作者：
Harstrick, Andreas
影响因子：
8.8
作者：
Jimeno, A.;Kulesza, P.;Hidalgo, M.
通讯作者：
Hidalgo, M.