癌症治疗靶点的鉴定:蛋白质组学技术和策略是成功的关键

R. Govekar
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摘要

随着“组学”领域的出现,生物学开始了一个系统的全球细胞分子分析的新时代。不同的“组学”方法已被广泛用于识别生物标志物,以更好地诊断和预后,治疗策略和监测对不同类型癌症的治疗反应。蛋白质组学是鉴定治疗靶点的首选方法。这是因为治疗性地调节蛋白质的表达、翻译后修饰和活性可以直接纠正致病细胞通路中的紊乱。本文回顾了肿瘤蛋白质组学的相关文献,以了解蛋白质组学技术和研究方法的发展对肿瘤治疗靶点确定的影响。肿瘤类型的多样性和病理上难以区分的肿瘤的分子异质性为评估蛋白质组学在识别药物靶点方面的优势提供了充分的挑战。该综述强调了通过凝胶或无凝胶方法在肿瘤和正常组织或耐药/敏感肿瘤组织中的比较蛋白质组学分析已经确定了分化蛋白,具有作为治疗靶点的潜力。此外,随着鉴定和定量蛋白质的蛋白质组学技术的发展,蛋白质功能分析的各种工具有助于目标鉴定的策略。这也表明,定量、功能和结构蛋白质组学的未来发展对于扩大对治疗靶点的研究是必要的。
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Identification of therapeutic targets for cancer: Proteomic technologies and strategies are the key to success
With the emergence of the field of ‘omics’ a new era of systematic global profiling of cellular molecules has been initiated in biology. Different ‘omics’ approaches have been extensively used to identify biomarkers for better diagnosis and prognosis, therapeutic strategies and monitoring response to therapy in diverse types of cancers. Proteomics is the approach of choice for identification of therapeutic targets. This is because therapeutic modulation of expression, post-translational modification and activity of a protein can directly rectify the derangement in the disease-causing cellular pathway. The current review scans literature on tumor proteomics to understand the influence of developments in proteomics technology and study approaches on identification of targets for therapy. Diversity of tumor types, molecular heterogeneity in pathologically indistinguishable tumors provides ample challenge to assess the strength of proteomics in identification of drug targets. The review highlights comparative proteomic profiling by gel-based or gel free approach, in tumor and normal tissues or chemo-resistant/sensitive tumor tissues have identified differentiator proteins, with potential as targetsas therapeutic targets. Further, along with evolution in proteomic technologies for identification and quantification of proteins, various tools for functional analysis of proteins have contributed to strategies for target identification. It also suggests that future advances in quantitative, functional and structural proteomics isare necessary to widen the search for therapeutic targets.
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