克罗恩病治疗中的靶向治疗和计算方法

IF 3.3 4区 医学 Q2 GENETICS & HEREDITY
Ajay Kumar Pandey, Sayali Mukherjee
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引用次数: 0

摘要

克罗恩病(CD)是一种慢性胃肠道炎症性疾病,由于其多因素病因和不同的治疗反应,在临床医学中提出了重大挑战。这篇综述探讨了导致乳糜泻的多种原因,包括通过全基因组关联研究(GWAS)确定的遗传易感性,该研究涉及扫描基因组中与乳糜泻风险相关的单核苷酸多态性,以及环境触发因素,如饮食和微生物组的改变。生物标志物,如粪便钙保护蛋白和活性蛋白(CRP),以及遗传标志物如NOD2突变,为诊断和治疗分层提供了关键工具。计算方法的进步,包括多组学分析和机器学习,增强了我们对CD病理生理学和治疗结果的理解。传统的治疗方法,包括免疫调节剂和生物制剂,如抗肿瘤坏死因子药物,为新的细胞因子靶向治疗奠定了基础,如IL-12/23抑制剂(如ustekinumab)和整合素抑制剂(如vedolizumab),旨在改善粘膜愈合和降低复发率。然而,由于CD的异质性和生物标志物验证的局限性,将个性化医疗整合到临床实践中仍然具有挑战性。预测性生物标志物与计算工具的整合使临床医生能够在个体水平上定制治疗,提高缓解率,最大限度地减少不良反应,并加强长期疾病控制。这些个性化的策略显示了将乳糜泻管理转向更有效的、针对患者的护理模式的希望。这篇综述强调了个性化治疗策略的潜力,利用分子和计算的见解,优化疾病管理和改善CD患者的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeted Therapies and Computational Approaches in the Management of Crohn's Disease.

Crohn's disease (CD), a chronic inflammatory disorder of the gastrointestinal tract, presents significant challenges in clinical medicine due to its multifactorial etiology and varied therapeutic responses. This review examines the diverse causes of CD, including genetic predispositions identified through genome-wide association studies (GWAS), which involve scanning the genome for single-nucleotide polymorphisms associated with CD risk, as well as environmental triggers, such as diet and alterations in the microbiome. Biomarkers, such as fecal calprotectin and Creactive protein (CRP), as well as genetic markers like NOD2 mutations, provide critical tools for diagnosis and treatment stratification. Advances in computational methodologies, including multiomics analyses and machine learning, have enhanced our understanding of CD pathophysiology and therapeutic outcomes. Traditional treatments, including immunomodulators and biologics, such as anti-TNF agents, have laid the groundwork for novel cytokine-targeted therapies, such as IL-12/23 inhibitors (e.g., ustekinumab) and integrin inhibitors (e.g., vedolizumab), which aim to improve mucosal healing and reduce relapse rates. However, integrating personalized medicine into clinical practice remains challenging due to the heterogeneity of CD and limitations in biomarker validation. The integration of predictive biomarkers with computational tools enables clinicians to tailor therapy at the individual level, improving remission rates, minimizing adverse effects, and enhancing long-term disease control. These personalized strategies show promise in shifting CD management toward a more effective, patient-specific model of care. This review underscores the potential of personalized therapeutic strategies, leveraging molecular and computational insights, to optimize disease management and improve patient outcomes in CD.

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来源期刊
Current gene therapy
Current gene therapy 医学-遗传学
CiteScore
6.70
自引率
2.80%
发文量
46
期刊介绍: Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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