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Assessment of the Viability of CRISPR/Cas9 Application in Immunotherapy for Hepatocellular
- 1 The Hong Kong Polytechnic University, Hong Kong, China
* Author to whom correspondence should be addressed.
Abstract
Liver cancer affects a significant number of individuals annually, and it ranks as the third leading cause of cancer-related deaths. In the past decade, significant advances have been brought to provide more options for treating hepatocellular carcinoma (HCC). However, the development of treatment resistance in HCC patients raises challenges for clinicians in managing this malignant tumor. The use of the CRISPR/Cas9 system to identify genes that enhance clinical response in HCC patients lays a solid foundation for personalized treatment. This article summarizes the current understanding of using the CRISPR/Cas9 system in cancer therapy, particularly emphasizing its application to HCC. This review presents examples and relative mechanisms of using CRISPR/Cas9 with immune checkpoint inhibitors to control tumor cell growth and discusses how CRISPR/Cas9 can prevent viral hepatitis from progressing to HCC. This review aims to improve patient prognosis and fundamentally transform the treatment landscape of HCC by reviewing the prospects and current status of CRISPR technology in the treatment of HCC
Keywords
Hepatocellular carcinoma, genome engineering, CRISPR/Cas9, cancer immunotherapy
[1]. Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2024). Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229-263.
[2]. Sayiner, M., Golabi, P., & Younossi, Z. M. (2019). Disease burden of hepatocellular carcinoma: A global perspective. Digestive Diseases and Sciences, 64(4), 910-917.
[3]. Li, X., Lovell, J. F., Yoon, J., & Chen, X. (2020). Clinical development and potential of photothermal and photodynamic therapies for cancer. Nature Reviews Clinical Oncology, 17(11), 657-674.
[4]. Nagarsheth, N., Wicha, M. S., & Zou, W. (2017). Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nature Reviews Immunology, 17(9), 559-572.
[5]. Xie, Y., et al. (2024). Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer. Cell Death & Disease, 15(2), 110. https://doi.org/10.1038/s41419-024-06493-0
[6]. Jiang, C., Meng, L., Yang, B., & Luo, X. (2020). Application of CRISPR/Cas9 gene editing technique in the study of cancer treatment. Clinical Genetics, 97(1), 73-88.
[7]. Liu, B., Saber, A., & Haisma, H. J. (2019). CRISPR/Cas9: A powerful tool for identification of new targets for cancer treatment. Drug Discovery Today, 24(4), 955-970. https://doi.org/10.1016/j.drudis.2019.02.011
[8]. Yu, S., et al. (2023). Research progress and application of the CRISPR/Cas9 gene-editing technology based on hepatocellular carcinoma. Asian Journal of Pharmaceutical Sciences, 18(4), 100828.
[9]. Feng, X., Li, Z., Liu, Y., Chen, D., & Zhou, Z. (2024). CRISPR/Cas9 technology for advancements in cancer immunotherapy: From uncovering regulatory mechanisms to therapeutic applications. Experimental Hematology & Oncology, 13(1), 102.
[10]. Makarova, K. S., et al. (2011). Evolution and classification of the CRISPR–Cas systems. Nature Reviews Microbiology, 9(6), 467-477.
[11]. Ogunwobi, O. O., et al. (2019). Mechanisms of hepatocellular carcinoma progression. World Journal of Gastroenterology, 25(19), 2279-2293.
[12]. Van Doorn, D. J., Takkenberg, R. B., & Klümpen, H. J. (2020). Immune checkpoint inhibitors in hepatocellular carcinoma: An overview. Pharmaceuticals (Basel), 14(1).
[13]. Cyranoski, D. (2016). CRISPR gene-editing tested in a person for the first time. Nature, 539(7630), 479.
[14]. Xu, Y., Chen, C., Guo, Y., Hu, S., & Sun, Z. (2022). Effect of CRISPR/Cas9-edited PD-1/PD-L1 on tumor immunity and immunotherapy. Frontiers in Immunology, 13, 848327.
[15]. Feng, Z., Rong, P., & Wang, W. (2020). Meta-analysis of the efficacy and safety of PD-1/PD-L1 inhibitors administered alone or in combination with anti-VEGF agents in advanced hepatocellular carcinoma. Gut, 69(10), 1904-1906.
[16]. Bartosh, U. I., Dome, A. S., Zhukova, N. V., et al. (2023). CRISPR/Cas9 as a new antiviral strategy for treating hepatitis viral infections. International Journal of Molecular Sciences, 25(1), 334.
[17]. Kostyusheva, A. P., Kostyushev, D. S., Brezgin, S. A., Zarifyan, D. N., Volchkova, E. V., & Chulanov, V. P. (2019). Small molecular inhibitors of DNA double strand break repair pathways increase the anti-HBV activity of CRISPR/Cas9. Molecular Biology, 53(2), 274-285.
[18]. Price, A. A., Sampson, T. R., Ratner, H. K., Grakoui, A., & Weiss, D. S. (2015). Cas9-mediated targeting of viral RNA in eukaryotic cells. Proceedings of the National Academy of Sciences, 112(19), 6164-6169.
Cite this article
Wei,Y. (2025). Assessment of the Viability of CRISPR/Cas9 Application in Immunotherapy for Hepatocellular. Theoretical and Natural Science,90,32-37.
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Volume title: Proceedings of ICMMGH 2025 Workshop: Computational Modelling in Biology and Medicine
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