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基础研究的临床意义:探索空间组学在泌尿肿瘤学中的变革潜力

Clinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology.

作者信息

Figiel Sandy, Bates Anthony, Braun David A, Eapen Renu, Eckstein Markus, Manley Brandon J, Milowsky Matthew I, Mitchell Tom J, Bryant Richard J, Sfakianos John P, Lamb Alastair D

机构信息

Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.

Department of Urology, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

出版信息

Eur Urol. 2025 Jan;87(1):8-14. doi: 10.1016/j.eururo.2024.08.025. Epub 2024 Sep 2.

DOI:10.1016/j.eururo.2024.08.025
PMID:39227262
Abstract

New spatial molecular technologies are poised to transform our understanding and treatment of urological cancers. By mapping the spatial molecular architecture of tumours, these platforms uncover the complex heterogeneity within and around individual malignancies, offering novel insights into disease development, progression, diagnosis, and treatment. They enable tracking of clonal phylogenetics in situ and immune-cell interactions in the tumour microenvironment. A whole transcriptome/genome/proteome-level spatial analysis is hypothesis generating, particularly in the areas of risk stratification and precision medicine. Current challenges include reagent costs, harmonisation of protocols, and computational demands. Nonetheless, the evolving landscape of the technology and evolving machine learning applications have the potential to overcome these barriers, pushing towards a future of personalised cancer therapy, leveraging detailed spatial cellular and molecular data. PATIENT SUMMARY: Tumours are complex and contain many different components. Although we have been able to observe some of these differences visually under the microscope, until recently, we have not been able to observe the genetic changes that underpin cancer development. Scientists are now able to explore molecular/genetic differences using approaches such as "spatial transcriptomics" and "spatial proteomics", which allow them to see genetic and cellular variation across a region of normal and cancerous tissue without destroying the tissue architecture. Currently, these technologies are limited by high associated costs, and a need for powerful and complex computational analysis workflows. Future advancements and results through these new technologies may assist patients and their doctors as they make decisions about treating their cancer.

摘要

新的空间分子技术有望改变我们对泌尿系统癌症的理解和治疗方式。通过绘制肿瘤的空间分子结构,这些平台揭示了单个恶性肿瘤内部和周围复杂的异质性,为疾病的发展、进展、诊断和治疗提供了新的见解。它们能够原位追踪克隆系统发育以及肿瘤微环境中的免疫细胞相互作用。全转录组/基因组/蛋白质组水平的空间分析正在催生新的假设,尤其是在风险分层和精准医学领域。当前的挑战包括试剂成本、方案的统一以及计算需求。尽管如此,该技术不断发展的态势以及不断演进的机器学习应用有潜力克服这些障碍,推动个性化癌症治疗的未来发展,充分利用详细的空间细胞和分子数据。患者总结:肿瘤是复杂的,包含许多不同的成分。尽管我们已经能够在显微镜下直观地观察到其中一些差异,但直到最近,我们还无法观察到支撑癌症发展的基因变化。科学家现在能够使用“空间转录组学”和“空间蛋白质组学”等方法探索分子/基因差异,这些方法使他们能够在不破坏组织结构的情况下观察正常组织和癌组织区域内的基因和细胞变异。目前,这些技术受到高相关成本以及对强大而复杂的计算分析工作流程的需求的限制。通过这些新技术取得的未来进展和成果可能会在患者及其医生做出癌症治疗决策时提供帮助。

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