Mapping molecular networks using proteomics: A vision for patient-tailored combination therapy
Mapping molecular networks using proteomics: A vision for patient-tailored combination therapy
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DOI：
10.1200/jco.2005.02.509
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发表时间：
2005-05-20
影响因子：
45.3
通讯作者：
Liotta, LA
中科院分区：
文献类型：
--
作者：
Petricoin, EF;Bichsel, VE;Liotta, LA
在体内绘制肿瘤细胞蛋白网络对于实现针对患者的分子治疗至关重要。癌症可以被定义为细胞内和细胞外信号级联网络的失调或过度活跃。这些蛋白质信号通路是分子治疗的最终目标。每个病人的肿瘤可能是由一系列不同的分子致病性缺陷驱动的。因此，对于任何单一分子靶向治疗，只有一部分癌症患者可能有反应。个体化治疗，即根据肿瘤分子特征定制治疗方案，可能是解决这一困境的办法。直到最近，该领域还缺乏基因组和蛋白质组水平的分子分析技术。新兴的蛋白质组学技术与基因组分析相结合，有望满足这一需求，并使分子分层的临床应用成为现实。激酶驱动信号网络的激活状态包含与癌症发病机制和治疗靶点选择相关的重要信息。蛋白质组学技术提供了一种量化激酶途径状态的方法，并提供了基因阵列无法获得的翻译后磷酸化数据。案例研究使用临床研究标本提供，以显示产生个性化治疗所需的关键信息的可行性。这种技术可以揭示潜在的新的通路相互联系，包括原发性和转移性病变之间的差异。我们提供了一个基于临床组织材料中磷酸化终点的蛋白质组学定位的个性化组合治疗的愿景。(c) 2005年由美国临床肿瘤学会出版。
Mapping tumor cell protein networks in vivo will be critical for realizing the promise of patient-tailored molecular therapy. Cancer can be defined as a dysregulation or hyperactivity in the network of intracellular and extracellular signaling cascades. These protein signaling circuits are the ultimate targets of molecular therapy. Each patient's tumor may be driven by a distinct series of molecular pathogenic defects. Thus, for any single molecular targeted therapy, only a subset of cancer patients may respond. Individualization of therapy, which tailors a therapeutic regimen to a tumor molecular portrait, may be the solution to this dilemma. Until recently, the field lacked the technology for molecular profiling at the genomic and proteomic level. Emerging proteomic technology, used concomitantly with genomic analysis, promises to meet this need and bring to reality the clinical adoption of molecular stratification. The activation state of kinase-driven signal networks contains important information relative to cancer pathogenesis and therapeutic target selection. Proteomic technology offers a means to quantify the state of kinase pathways, and provides post-translational phosphorylation data not obtainable by gene arrays. Case studies using clinical research specimens are provided to show the feasibility of generating the critical information needed to individualize therapy. Such technology can reveal potential new pathway interconnections, including differences between primary and metastatic lesions. We provide a vision for individualized combinatorial therapy based on proteomic mapping of phosphorylation end points in clinical tissue material. (c) 2005 by American Society of Clinical Oncology.