Hashim Hashim Talib, Alhatemi Ahmed Qasim Mohammed, Fatima Tehreem, Haque Tahmina, Sulaiman Fatimah Abdullah, Ganim Mohammed, Abdullah Muhanned Ahmed, Kadhum Rawaa Awad, Al-Obaidi Ahmed Dheyaa, Al-Obaidi Ammar
College of Medicine, University of Warith Al-Anbiyaa, Karbala, Iraq.
Al-Nassiryah Teaching Hospital, Nassiryah, Thi Qar, Iraq.
Discov Oncol. 2025 Apr 23;16(1):596. doi: 10.1007/s12672-025-02231-w.
Pancreatic cancer is one of the main causes of cancer-related deaths, especially pancreatic ductal adenocarcinoma, and it's characterized by a poor prognosis. The KRAS gene mutation is prevalent in about 85% of pancreatic cancer cases, which is a significant factor in the pathogenesis and development of pancreatic cancer, impacting cellular tumor growth, survival, and metastasis. The targeted disruption of mutant KRAS variants through the application of various CRISPR systems has led to a marked reduction in cell viability and proliferation in vitro, accompanied by significant inhibition of tumor growth in vivo.
This systematic study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search of PubMed, Google Scholar, and PLOS One for original research articles published up to June 2024. Studies included those involving CRISPR-Cas9 gene editing targeting KRAS mutations in human or animal models of pancreatic cancer. Data collection and quality assessment were performed independently by two reviewers.
The review identified numerous studies demonstrating the efficacy of CRISPR-Cas9 in targeting KRAS mutations. Results showed significant reductions in KRAS transcript levels, decreased tumor progression, and improved survival rates in experimental models. However, challenges such as off-target effects and efficient delivery methods were noted.
CRISPR-Cas9 gene editing shows significant promise as a therapeutic strategy for targeting KRAS mutations in pancreatic cancer. While the technology has demonstrated potential in preclinical studies, further research is needed to address challenges related to specificity, delivery, and long-term effects to facilitate its clinical application.
胰腺癌是癌症相关死亡的主要原因之一，尤其是胰腺导管腺癌，其预后较差。KRAS基因突变在约85%的胰腺癌病例中普遍存在，这是胰腺癌发病机制和发展的一个重要因素，影响细胞肿瘤的生长、存活和转移。通过应用各种CRISPR系统对突变型KRAS变体进行靶向破坏，已导致体外细胞活力和增殖显著降低，同时体内肿瘤生长受到显著抑制。
本系统研究遵循系统评价和Meta分析的首选报告项目指南，全面检索了截至2024年6月发表的原始研究文章的PubMed、谷歌学术和PLOS One。研究包括在胰腺癌的人类或动物模型中涉及靶向KRAS突变的CRISPR-Cas9基因编辑的研究。数据收集和质量评估由两名审稿人独立进行。
该综述确定了大量研究，证明了CRISPR-Cas9在靶向KRAS突变方面的有效性。结果显示，在实验模型中，KRAS转录水平显著降低，肿瘤进展减缓，存活率提高。然而，也注意到了脱靶效应和有效递送方法等挑战。
CRISPR-Cas9基因编辑作为一种靶向胰腺癌KRAS突变的治疗策略显示出巨大的前景。虽然该技术在临床前研究中已显示出潜力，但需要进一步研究以解决与特异性、递送和长期效应相关的挑战，以促进其临床应用。
