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首页> 外文期刊>Nature reviews. Urology >Personalization of prostate cancer therapy through phosphoproteomics
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Personalization of prostate cancer therapy through phosphoproteomics

机译：通过磷蛋白组的前列腺癌治疗的个性化

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Castration-resistant prostate cancer (CRPC) remains incurable despite the approval of several new treatments. Identification of new biomarkers and therapeutic targets to enable personalization of CRPC therapy, with the aim of maximizing therapeutic responses and minimizing toxicity in patients, is urgently needed. Prostate cancer progression and therapeutic resistance are frequently driven by aberrantly activated kinase signalling pathways that are amenable to pharmacological inhibition. Personalized phosphoproteomics, which enables the analysis of signalling networks in individual tumours, is a promising approach to advance personalized therapy by discovering biomarkers of pathway activity and clinically actionable targets. Several technologies for global and targeted phosphoproteomic analysis exist, each with its own strengths and shortcomings. Global discovery phosphoproteomics is predominantly conducted using liquid chromatography-tandem mass spectrometry coupled with data-dependent or data-independent acquisition technologies. Multiplexed targeted phosphoproteomics can be divided into platforms based on mass spectrometry or antibodies, including selected or parallel reaction monitoring and triggered by offset, multiplexed, accurate mass, high-resolution, absolute quantification (known as TOMAHAQ) or forward-phase or reverse-phase protein arrays, respectively. Several obstacles still need to be overcome before the full potential of phosphoproteomics can be realized in routine clinical practice, but a future phosphoproteomics-centric trans-omic profiling approach should enable optimized personalized CRPC management through improved biomarkers and targeted treatments.
机译：尽管批准了几种新治疗方法，抵抗性前列腺癌（CRPC）仍然是可行的。鉴定新的生物标志物和治疗目标，以使人类的性能疗法能够最大限度地提高治疗反应和最小化患者毒性的目的是迫切需要。前列腺癌进展和治疗抗性经常通过可见的激活激酶信号传导途径驱动，所述激活激酶信号传导途径可用于药理学抑制。个性化磷蛋白酶，其能够分析单个肿瘤中的信号网络，是通过发现途径活动和临床可行目标的生物标志物来推进个性化治疗的有希望的方法。存在若干全球和靶向磷蛋白酶分析的技术，每个技术都具有自己的优势和缺点。使用液相色谱 - 串联质谱法与数据相关或数据无关的采集技术耦合的全局发现磷蛋白酶。多路复用的靶向磷蛋白酶可以基于质谱或抗体分为平台，包括选择或平行的反应监测，并通过偏移，多路复用，精确的质量，高分辨率，绝对量化（称为Tomahaq）或正常或反向阶段触发分别是蛋白质阵列。在常规临床实践中可以实现磷蛋白蛋白质的全部潜力之前，仍然需要克服几种障碍，但是未来的磷蛋白质中心的反式OMIC分析方法应通过改善的生物标志物和有针对性的治疗来实现优化的个性化CRPC管理。

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