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

被引:0
作者
Kermanshahi, Atefeh Zamani [1 ,2 ]
Ebrahimi, Fatemeh [1 ,4 ]
Taherpoor, Ahmad [5 ,6 ]
Eslami, Narges [7 ,8 ]
Baghi, Hossein Bannazadeh [1 ,2 ,3 ]
机构
[1] Tabriz Univ Med Sci, Infect & Trop Dis Res Ctr, Tabriz 516615731, Iran
[2] Tabriz Univ Med Sci, Immunol Res Ctr, Tabriz, Iran
[3] Tabriz Univ Med Sci, Fac Med, Dept Virol, Tabriz, Iran
[4] Univ Tehran Med Sci, Sch Publ Hlth, Dept Virol, Tehran, Iran
[5] Mashhad Univ Med Sci, Fac Med, Dept Clin Bacteriol & Virol, Mashhad, Iran
[6] Mashhad Univ Med Sci, Antimicrobial Res Ctr, Mashhad, Iran
[7] Guilan Univ Med Sci, Gastrointestinal & Liver Dis Res Ctr, Rasht, Iran
[8] Guilan Univ Med Sci, Sch Med, Dept Microbiol, Rasht, Iran
关键词
HPV; CRISPR-Cas9; Gene editing; Oncogenes; Tumor suppressors; HUMAN-PAPILLOMAVIRUS TYPE-16; CERVICAL-CANCER; COMPLEX-FORMATION; IN-VITRO; GENE; E6; SYSTEM; IMMUNOTHERAPY; STRATEGIES; CARCINOMA;
D O I
10.1186/s12985-025-02783-x
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
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页数:17
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共 164 条
[111]   Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge [J].
Pesut, Ena ;
Dukic, Anamaria ;
Lulic, Lucija ;
Skelin, Josipa ;
Simic, Ivana ;
Milutin Gasperov, Nina ;
Tomaic, Vjekoslav ;
Sabol, Ivan ;
Grce, Magdalena .
VIRUSES-BASEL, 2021, 13 (11)
[112]   Strategies to overcome the main challenges of the use of CRISPR/Cas9 as a replacement for cancer therapy [J].
Rasul, Mohammed Fatih ;
Hussen, Bashdar Mahmud ;
Salihi, Abbas ;
Ismael, Bnar Saleh ;
Jalal, Paywast Jamal ;
Zanichelli, Anna ;
Jamali, Elena ;
Baniahmad, Aria ;
Ghafouri-Fard, Soudeh ;
Basiri, Abbas ;
Taheri, Mohammad .
MOLECULAR CANCER, 2022, 21 (01)
[113]   Applications of CRISPR-Cas9 for advancing precision medicine in oncology: from target discovery to disease modeling [J].
Ravichandran, Mirunalini ;
Maddalo, Danilo .
FRONTIERS IN GENETICS, 2023, 14
[114]  
Riedel Maria, 2021, Oncotarget, V12, P1956, DOI 10.18632/oncotarget.27997
[115]   Epidemiology and incidence of HPV-related cancers of the head and neck [J].
Roman, Benjamin R. ;
Aragones, Abraham .
JOURNAL OF SURGICAL ONCOLOGY, 2021, 124 (06) :920-922
[116]   Cancer immunotherapies: advances and bottlenecks [J].
Rui, Rui ;
Zhou, Liqun ;
He, Shiming .
FRONTIERS IN IMMUNOLOGY, 2023, 14
[117]   CRISPR/Cas9-mediated PD-1 disruption enhances anti-tumor efficacy of human chimeric antigen receptor T cells [J].
Rupp, Levi J. ;
Schumann, Kathrin ;
Roybal, Kole T. ;
Gate, Rachel E. ;
Ye, Chun J. ;
Lim, Wendell A. ;
Marson, Alexander .
SCIENTIFIC REPORTS, 2017, 7
[118]   Epigenetic modifications: Key players in cancer heterogeneity and drug resistance [J].
Sadida, Hana Q. ;
Abdulla, Alanoud ;
Al Marzooqi, Sara ;
Hashem, Sheema ;
Macha, Muzafar A. ;
Akil, Ammira S. Al-Shabeeb ;
Bhat, Ajaz A. .
TRANSLATIONAL ONCOLOGY, 2024, 39
[119]   p21 suppresses inflammation and tumorigenesis on pRB-deficient stratified epithelia [J].
Saiz-Ladera, C. ;
Lara, M. F. ;
Garin, M. ;
Ruiz, S. ;
Santos, M. ;
Lorz, C. ;
Garcia-Escudero, R. ;
Martinez-Fernandez, M. ;
Bravo, A. ;
Fernandez-Capetillo, O. ;
Segrelles, C. ;
Paramio, J. M. .
ONCOGENE, 2014, 33 (37) :4599-4612
[120]   THE HPV-16 E6 AND E6-AP COMPLEX FUNCTIONS AS A UBIQUITIN-PROTEIN LIGASE IN THE UBIQUITINATION OF P53 [J].
SCHEFFNER, M ;
HUIBREGTSE, JM ;
VIERSTRA, RD ;
HOWLEY, PM .
CELL, 1993, 75 (03) :495-505