The role of CRISPR genome editing technology in the treatment of pancreatic cancer
The role of CRISPR genome editing technology in the treatment of pancreatic cancer
Farshid Fathabadi,1,*
1. Laboratory Science Research Center, School of Paramedecine, Golestan University of Medical Science
Introduction: Pancreatic cancer is the twelfth most common cancer worldwide and the seventh leading cause of cancer death, with more than 95% of cases associated with pancreatic ductal adenocarcinoma (PDAC). Generally, only less than 10% of patients with pancreatic cancer have an overall survival of more than five years; Consequently, the diagnosis and treatment of pancreatic cancer have become one of the main challenges for researchers. The main treatment options available to patients include; Surgery, chemotherapy, and radiotherapy that; even after treatment by these methods, the disease tends to return after two years, but today newer methods are offered to treat this disease; CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) genome editing technology is one of these methods. As a new approach, CRISPR can use “Cas” proteins that have endonuclease activity to cut the DNA according to the instructions given to them by the sgRNA and modify the gene. CRISPR has become a high-potential tool for gene therapy for many diseases; This technology has lower cost, higher efficiency, and less complexity than other gene therapy methods. Due to the critical role of genetics in tumor formation and development, the use of this tool is essential.
Methods: This article is a review, and we identified its documents by searching for the keywords “pancreatic cancer”, “CRISPR/Cas9” and “CRISPR Technology” in international databases such as “PubMed”, “Google Scholar”, “Scopus”, and “ScienceDirect”. The search period was limited to 2016 to 2021. We found about 55 articles in the initial search, which after further examination, we left out 22 articles with less relevance to the subject. We thoroughly studied 18 articles relevant to the subject from the remaining cases and extracted their results.
Results: The most common mutations in pancreatic cancer are related to KRAS, TP53, SMAD4, CDKN2A genes, which KRAS mutant gene is one of the influential factors in the development of pancreatic cancer; More than 90% of patients with PDAC have this gene mutation, of which the single-site mutation (KrasG12D) is the most common. Both CRISPR/Cas13a and CRISPR/Cas9 systems can play a potentially influential role in preventing the spread of disease by directing sgRNAs and destroying the KRAS G12D mutant gene. Knockdown of HIF-1a, which causes cancer cells to survive under hypoxia, by the CRISPR/Cas9 system effectively inhibits tumor metastasis and increases patient survival. In a study, the ABCG2 gene was identified as the most stable drug resistance gene in patients chemotherapy; The knockout of this gene by CRISPR can help increase sensitivity and reduce resistance to chemotherapy drugs for pancreatic cancer, including Oxaliplatin. The PSMA6 gene in the PDAC acts as an oncogene, and the CRISPR system can induce apoptosis of pancreatic cancer cells by inhibiting the expression of this gene. Also, in some studies, targeting and deleting the PRMT5 gene by CRISPR technology, combined with Gemcitabine, one of the first-line drugs in pancreatic cancer chemotherapy, had a synergistic effect and inhibited tumor growth, and induced cancer cells death that was detected in both in-vivo and in-vitro studies.
Conclusion: According to the role of various genetic and epigenetic changes in the pathogenesis of pancreatic cancer, CRISPR genome editing technology can be used as a practical and high-potential treatment approach to cure this disease and increase patient survival. However, due to the novelty of this technology, there is a need for more detailed studies and finding more effective options for genetic manipulation in this disease.