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人乳头瘤病毒驱动的癌症:一个迫在眉睫的威胁以及CRISPR/Cas9用于靶向治疗的潜力

HPV-driven cancers: a looming threat and the potential of CRISPR/Cas9 for targeted therapy.

作者信息

Kermanshahi Atefeh Zamani, Ebrahimi Fatemeh, Taherpoor Ahmad, Eslami Narges, Baghi Hossein Bannazadeh

机构信息

Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, 5166/15731, Iran.

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

出版信息

Virol J. 2025 May 22;22(1):156. doi: 10.1186/s12985-025-02783-x.

Abstract

Cervical and other anogenital malignancies are largely caused by E6 and E7 oncogenes of high-risk human papillomaviruses (HPVs), which inhibit important tumor suppressors like p53 and pRb when they are persistently activated. The main goal of traditional treatments is to physically or chemically kill cancer cells, but they frequently only offer temporary relief, have serious side effects, and have a high risk of recurrence. Exploring the efficacy and accuracy of CRISPR-Cas9 gene editing in both inducing death in HPV-infected cancer cells and restoring the activity of tumor suppressors is our main goal. In this study, we propose a novel precision oncology strategy that targets and inhibits the detrimental effects of the E6 and E7 oncogenes using the CRISPR-Cas9 gene editing system. In order to do this, we create unique guide RNAs that target the integrated HPV DNA and reactivate p53 and pRb. Reactivation is meant to halt aberrant cell development and restart the cell's natural dying pathways. This review discusses the potential of CRISPR/Cas9 in targeting HPV oncogenes, with a focus on studies that have demonstrated its promise in cancer treatment. Given the absence of a definitive treatment for papillomavirus infection and its subsequent association with various cancers, future clinical trials and experimental investigations appear essential to establish and evaluate the therapeutic potential of CRISPR-based approaches. This approach provides a less invasive alternative to conventional treatments and opens the door to personalized care that considers the genetic makeup of each patient's tumor.

摘要

宫颈癌和其他肛门生殖器恶性肿瘤在很大程度上是由高危型人乳头瘤病毒(HPV)的E6和E7癌基因引起的,当这些基因持续激活时,它们会抑制重要的肿瘤抑制因子,如p53和pRb。传统治疗的主要目标是通过物理或化学方法杀死癌细胞,但这些方法往往只能提供暂时缓解,伴有严重副作用,且复发风险高。我们的主要目标是探索CRISPR-Cas9基因编辑在诱导HPV感染的癌细胞死亡以及恢复肿瘤抑制因子活性方面的有效性和准确性。在本研究中,我们提出了一种新型的精准肿瘤学策略,即使用CRISPR-Cas9基因编辑系统靶向并抑制E6和E7癌基因的有害作用。为此,我们设计了独特的导向RNA,靶向整合的HPV DNA并重新激活p53和pRb。重新激活旨在阻止异常细胞发育并重启细胞的自然死亡途径。本综述讨论了CRISPR/Cas9靶向HPV癌基因的潜力,重点关注已证明其在癌症治疗中有前景的研究。鉴于目前尚无针对乳头瘤病毒感染及其后续引发的各种癌症的确切治疗方法,未来的临床试验和实验研究对于确立和评估基于CRISPR的治疗方法的潜力似乎至关重要。这种方法为传统治疗提供了一种侵入性较小的替代方案,并为考虑每个患者肿瘤基因构成的个性化医疗打开了大门。

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