Clinical development prospects of siRNA drugs for tumor therapy: analysis of clinical trial registration data from 2004 to 2024.

IF 4.8 2区医学 Q1 PHARMACOLOGY & PHARMACY

Frontiers in Pharmacology Pub Date : 2025-09-17 eCollection Date: 2025-01-01 DOI:10.3389/fphar.2025.1637958

Cai-E Wang, Delong Zhen, Lukui Yang, Guifang Li

{"title":"Clinical development prospects of siRNA drugs for tumor therapy: analysis of clinical trial registration data from 2004 to 2024.","authors":"Cai-E Wang, Delong Zhen, Lukui Yang, Guifang Li","doi":"10.3389/fphar.2025.1637958","DOIUrl":null,"url":null,"abstract":"Background: This study systematically compares clinical trial patterns of siRNA drugs in oncology and non-oncology, aiming to inform optimized R&D strategies for oncology.Methods: Trial phases, sponsor countries, biomarkers, and targets were analyzed for global siRNA trials (2004-2024).Results: Non-oncology trial dominated (90% of 424 trials), peaking in 2021 (64 trials), and yielded 6 approved drugs for metabolic/genetic diseases. Key non-oncology targets included PCSK9 and HBV. Oncology trials initiated later, primarily focusing on phase I/II studies (60% phase I), targeting solid tumors (40%) and CSF2-related therapies (40%). Clinical trial activity in China commenced in 2019, demonstrating acceleration in 2023, yet overall trial volume remains lower than global benchmarks. Cross-target analysis has pinpointed PTGS2 and TGFB1 as shared targets, indicating the possibility for combination therapy.Conclusion: Overcoming technical challenges (e.g., targeted delivery) and exploiting multi-target synergies are critical to expanding siRNAs applications in oncology. Success in non-oncology settings demonstrates the translational potential of siRNA technology, however, oncology requires tailored strategies to address complex tumor biology and delivery barriers.","PeriodicalId":12491,"journal":{"name":"Frontiers in Pharmacology","volume":"16 ","pages":"1637958"},"PeriodicalIF":4.8000,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12484142/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Pharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fphar.2025.1637958","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: This study systematically compares clinical trial patterns of siRNA drugs in oncology and non-oncology, aiming to inform optimized R&D strategies for oncology.

Methods: Trial phases, sponsor countries, biomarkers, and targets were analyzed for global siRNA trials (2004-2024).

Results: Non-oncology trial dominated (90% of 424 trials), peaking in 2021 (64 trials), and yielded 6 approved drugs for metabolic/genetic diseases. Key non-oncology targets included PCSK9 and HBV. Oncology trials initiated later, primarily focusing on phase I/II studies (60% phase I), targeting solid tumors (40%) and CSF2-related therapies (40%). Clinical trial activity in China commenced in 2019, demonstrating acceleration in 2023, yet overall trial volume remains lower than global benchmarks. Cross-target analysis has pinpointed PTGS2 and TGFB1 as shared targets, indicating the possibility for combination therapy.

Conclusion: Overcoming technical challenges (e.g., targeted delivery) and exploiting multi-target synergies are critical to expanding siRNAs applications in oncology. Success in non-oncology settings demonstrates the translational potential of siRNA technology, however, oncology requires tailored strategies to address complex tumor biology and delivery barriers.

查看原文本刊更多论文

肿瘤治疗siRNA药物临床发展前景：2004 - 2024年临床试验注册数据分析

背景：本研究系统比较了siRNA药物在肿瘤和非肿瘤领域的临床试验模式，旨在为优化肿瘤领域的研发策略提供依据。方法：分析2004-2024年全球siRNA试验的试验阶段、申办国、生物标志物和靶点。结果：非肿瘤学试验占主导地位（424项试验中占90%），在2021年达到峰值（64项试验），获得6种代谢/遗传疾病药物的批准。关键的非肿瘤靶点包括PCSK9和HBV。肿瘤试验开始较晚，主要集中在I/II期研究（60%为I期），针对实体肿瘤（40%）和csf2相关治疗（40%）。中国的临床试验活动于2019年开始，并在2023年加速，但总体试验量仍低于全球基准。交叉靶点分析已经确定PTGS2和TGFB1是共同靶点，表明联合治疗的可能性。结论：克服技术挑战（如靶向递送）和利用多靶点协同作用对于扩大sirna在肿瘤学中的应用至关重要。在非肿瘤学环境中的成功证明了siRNA技术的转化潜力，然而，肿瘤学需要量身定制的策略来解决复杂的肿瘤生物学和传递障碍。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Frontiers in Pharmacology PHARMACOLOGY & PHARMACY-

CiteScore

7.80

自引率

8.90%

发文量

5163

审稿时长

14 weeks

期刊介绍： Frontiers in Pharmacology is a leading journal in its field, publishing rigorously peer-reviewed research across disciplines, including basic and clinical pharmacology, medicinal chemistry, pharmacy and toxicology. Field Chief Editor Heike Wulff at UC Davis is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.