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癌症的靶向治疗 - 临床组织中新型蛋白质分析技术带来的挑战与机遇。

Targeted therapies in cancer - challenges and chances offered by newly developed techniques for protein analysis in clinical tissues.

机构信息

Department of Pathology, Technische Universität München, Munich, Germany.

出版信息

J Cancer. 2010 Dec 19;2:26-35. doi: 10.7150/jca.2.26.

Abstract

In recent years, new anticancer therapies have accompanied the classical approaches of surgery and radio- and chemotherapy. These new forms of treatment aim to inhibit specific molecular targets namely altered or deregulated proteins, which offer the possibility of individualized therapies.The specificity and efficiency of these new approaches, however, bring about a number of challenges. First of all, it is essential to specifically identify and quantify protein targets in tumor tissues for the reasonable use of such targeted therapies. Additionally, it has become even more obvious in recent years that the presence of a target protein is not always sufficient to predict the outcome of targeted therapies. The deregulation of downstream signaling molecules might also play an important role in the success of such therapeutic approaches. For these reasons, the analysis of tumor-specific protein expression profiles prior to therapy has been suggested as the most effective way to predict possible therapeutic results. To further elucidate signaling networks underlying cancer development and to identify new targets, it is necessary to implement tools that allow the rapid, precise, inexpensive and simultaneous analysis of many network components while requiring only a small amount of clinical material.Reverse phase protein microarray (RPPA) is a promising technology that meets these requirements while enabling the quantitative measurement of proteins. Together with recently developed protocols for the extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues, RPPA may provide the means to quantify therapeutic targets and diagnostic markers in the near future and reliably screen for new protein targets.With the possibility to quantitatively analyze DNA, RNA and protein from a single FFPE tissue sample, the methods are available for integrated patient profiling at all levels of gene expression, thus allowing optimal patient stratification for individualized therapies.

摘要

近年来,新的抗癌疗法伴随着经典的手术、放化疗方法出现。这些新的治疗形式旨在抑制特定的分子靶点,即改变或失调的蛋白质,这为个体化治疗提供了可能。然而,这些新方法的特异性和效率带来了许多挑战。首先,对于合理使用这些靶向治疗,必须特异性地识别和定量肿瘤组织中的蛋白质靶标。此外,近年来越来越明显的是,靶蛋白的存在并不总是足以预测靶向治疗的结果。下游信号分子的失调也可能在这些治疗方法的成功中发挥重要作用。出于这些原因,在治疗前分析肿瘤特异性蛋白质表达谱被认为是预测可能的治疗结果的最有效方法。为了进一步阐明癌症发展的信号网络并确定新的靶点,有必要实施能够快速、精确、经济且同时分析许多网络成分的工具,同时仅需要少量的临床材料。反相蛋白质微阵列(RPPA)是一种有前途的技术,满足这些要求,同时能够定量测量蛋白质。与最近开发的从福尔马林固定、石蜡包埋(FFPE)组织中提取蛋白质的方案一起,RPPA 可能在不久的将来提供定量测量治疗靶点和诊断标志物的方法,并可靠地筛选新的蛋白质靶点。通过从单个 FFPE 组织样本中定量分析 DNA、RNA 和蛋白质,这些方法可用于在所有基因表达水平上进行综合患者分析,从而为个体化治疗进行最佳的患者分层。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b240/3005552/8c796fee7982/jcav02p0026g01.jpg

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