Alhasso Bahjat, Shareef Abdulkareem, Baldaniya Lalji, Oweis Rami, Jyothi Renuka, Singh Udaybir, Sahoo Samir, Chauhan Ashish Singh, Sameer Hayder Naji, Yaseen Ahmed, Athab Zainab H, Adil Mohaned
College of Pharmacy, Alnoor University, Nineveh, Iraq.
Ahl al bayt University, Karbala, Iraq.
Iran J Basic Med Sci. 2025;28(10):1279-1300. doi: 10.22038/ijbms.2025.87531.18902.
Colorectal cancer (CRC) remains a significant global health challenge, necessitating advanced molecular therapies to improve outcomes. The CRISPR/Cas9 genome-editing platform has emerged as a transformative tool in CRC research, enabling precise genomic modifications to suppress tumor progression, enhance chemosensitivity, and modulate oncogenic pathways. This review highlights CRISPR/Cas9 applications in CRC models, including MC38 murine and CaCO-2 cell lines, where targeted gene edits demonstrate tumor-suppressive effects. For instance, Par3L protein knockout via CRISPR/Cas9 inhibits proliferation, induces apoptosis, and sensitizes cells to chemotherapy by regulating AMPK signaling. Additionally, AAV-mediated CRISPR editing shows promise in HPV16-driven CRC models. Despite its potential, clinical translation faces challenges such as off-target effects, immunogenicity, and delivery limitations. Advances in engineered CRISPR variants (e.g., xCas9, HypaCas9) and innovative delivery systems are refining specificity and efficacy. CRISPR/Cas9 also accelerates biomarker discovery, paving the way for precision oncology. Overcoming current barriers could revolutionize CRC therapeutics, offering personalized treatment paradigms.
结直肠癌(CRC)仍然是一项重大的全球健康挑战,需要先进的分子疗法来改善治疗效果。CRISPR/Cas9基因组编辑平台已成为CRC研究中的一种变革性工具,能够进行精确的基因组修饰以抑制肿瘤进展、增强化学敏感性并调节致癌途径。本综述重点介绍了CRISPR/Cas9在CRC模型中的应用,包括MC38小鼠模型和CaCO-2细胞系,在这些模型中,靶向基因编辑显示出肿瘤抑制作用。例如,通过CRISPR/Cas9敲除Par3L蛋白可抑制增殖、诱导凋亡,并通过调节AMPK信号通路使细胞对化疗敏感。此外,腺相关病毒(AAV)介导的CRISPR编辑在人乳头瘤病毒16(HPV16)驱动的CRC模型中显示出前景。尽管具有潜力,但临床转化面临着诸如脱靶效应、免疫原性和递送限制等挑战。工程化CRISPR变体(如xCas9、HypaCas9)和创新递送系统的进展正在提高特异性和疗效。CRISPR/Cas9还加速了生物标志物的发现,为精准肿瘤学铺平了道路。克服当前的障碍可能会彻底改变CRC治疗方法,提供个性化的治疗模式。