文章：

合成生物标志物：二十一世纪早期癌症检测的途径

Synthetic biomarkers: a twenty-first century path to early cancer detection

原文发布日期：2021-09-06

DOI: 10.1038/s41568-021-00389-3

类型: Review Article

开放获取: 否

英文摘要：

Detection of cancer at an early stage when it is still localized improves patient response to medical interventions for most cancer types. The success of screening tools such as cervical cytology to reduce mortality has spurred significant interest in new methods for early detection (for example, using non-invasive blood-based or biofluid-based biomarkers). Yet biomarkers shed from early lesions are limited by fundamental biological and mass transport barriers — such as short circulation times and blood dilution — that limit early detection. To address this issue, synthetic biomarkers are being developed. These represent an emerging class of diagnostics that deploy bioengineered sensors inside the body to query early-stage tumours and amplify disease signals to levels that could potentially exceed those of shed biomarkers. These strategies leverage design principles and advances from chemistry, synthetic biology and cell engineering. In this Review, we discuss the rationale for development of biofluid-based synthetic biomarkers. We examine how these strategies harness dysregulated features of tumours to amplify detection signals, use tumour-selective activation to increase specificity and leverage natural processing of bodily fluids (for example, blood, urine and proximal fluids) for easy detection. Finally, we highlight the challenges that exist for preclinical development and clinical translation of synthetic biomarker diagnostics.

摘要翻译： 

在大多数癌症类型中，当癌症仍处于局部局限的早期阶段时进行检测，可改善患者对医疗干预的反应。宫颈细胞学等筛查工具在降低死亡率方面的成功，激发了人们对早期检测新方法的浓厚兴趣（例如使用无创血液或体液生物标志物）。然而早期病变脱落的生物标志物受到基本生物学和质量传输障碍的限制——如循环时间短和血液稀释——这些限制了早期检测。为解决这一问题，合成生物标志物正在被开发。这类新兴诊断技术通过在体内部署生物工程传感器来探查早期肿瘤，并将疾病信号放大到可能超过脱落生物标志物的水平。这些策略融合了化学、合成生物学和细胞工程领域的设计原理与前沿进展。本综述将探讨开发基于体液的合成生物标志物的理论依据，分析这些策略如何利用肿瘤失调特征来放大检测信号，通过肿瘤选择性激活提高特异性，并借助体液（如血液、尿液及近端体液）的自然处理过程实现便捷检测。最后，我们将重点阐述合成生物标志物诊断技术在临床前开发和临床转化过程中面临的挑战。

原文链接：

Synthetic biomarkers: a twenty-first century path to early cancer detection