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[以系统性硬化症为例的纤维化的药理抑制:可能性与局限性]

[Pharmacological inhibition of fibrosis exemplified by systemic sclerosis : Possibilities and limits].

作者信息

Dashi Tobias, Bergmann Christina

机构信息

Medizinische Klinik 3-Rheumatologie, Universitätsklinikum Erlangen, Ulmenweg 18, D-91054, Erlangen, Deutschland.

Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-Universität Erlangen-Nürnberg and Uniklinikum Erlangen, Erlangen, Deutschland.

出版信息

Inn Med (Heidelb). 2025 Jun 27. doi: 10.1007/s00108-025-01925-1.

Abstract

Fibrotic diseases, such as cardiac, liver and lung fibrosis are a heterogeneous group of diseases with high mortality and fatality rates. Identifying cross-disease mechanisms is a potential strategy to find targets for these sometimes rare diseases. Additionally, it is necessary to consider disease-specific differences. Systemic sclerosis (SSc) is an autoimmune, fibrotic systemic disease. The possibilities and limitations of the pharmacological inhibition of fibrosis are exemplified and discussed in this article using SSc as an example. The focus of the article is on relevant pathogenetic aspects, new insights into known therapeutic principles, emerging developments "on the way to clinical application and ongoing studies", as well as an outlook on open questions. Continuing innovations in the field of molecular biological and computer-assisted analytical methods are enabling an increasingly more precise understanding of fibrosing tissue processes, serving as a basis for identifying new treatment strategies and approaches. Numerous targeted therapies are currently in phase 2/phase 3 clinical trials and are expected to be concluded in the coming years. Additionally, innovative options for deep B‑cell depletion are available for clinical testing; however, a "cure" for fibrotic diseases has not yet been achieved, and further questions remain on the research agenda.

摘要

纤维化疾病,如心脏、肝脏和肺部纤维化,是一组异质性疾病,具有高发病率和死亡率。识别跨疾病机制是为这些有时较为罕见的疾病寻找靶点的潜在策略。此外,有必要考虑疾病特异性差异。系统性硬化症(SSc)是一种自身免疫性、纤维化全身性疾病。本文以SSc为例,阐述并讨论了药物抑制纤维化的可能性和局限性。文章重点关注相关发病机制、对已知治疗原则的新见解、“在临床应用道路上”的新兴发展以及正在进行的研究,以及对未解决问题的展望。分子生物学和计算机辅助分析方法领域的持续创新使得对纤维化组织过程的理解越来越精确,为识别新的治疗策略和方法奠定了基础。目前许多靶向疗法正处于2期/3期临床试验阶段,预计将在未来几年完成。此外,深度B细胞清除的创新方案可供临床测试;然而,纤维化疾病的“治愈”尚未实现,研究议程上仍存在进一步的问题。

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