Efficacy of CRISPR-Cas9 Gene Editing for Targeting KRAS Mutations in Pancreatic Cancer: A systematic review

Background 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. Method This systematic study was 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. Results 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. Conclusion 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.