INTERNATIONAL CONGRESS OF
CancerGenetics
Advancements of Adenovirus-Based Gene Therapy in Colorectal Cancer
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Elham Kamalkazemi,1 Nasser Hashemi Goradel,2 Fatemeh Badipa,3 Efffat Alizadeh,4,*
1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
2. Department of Medical Biotechnology, Maragheh University of Medical Sciences, Maragheh, Iran
3. Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran, Department of Laboratory and Regenerative Medicine, University of Manchester, Manchester, United Kingdom
4. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
- Introduction: Despite the recent advances in controlling Colorectal cancer (CRC), CRC remains the second leading cause of cancer deaths in the world. Like the other cancers, genetic and epigenetic alterations are involved in CRC progression and pathogenesis. For example, Alteration in TP53, KRAS, BRAF expression are the most common types of mutations in CRC. Therefore, in comparison to conventional therapeutic approaches for the treatment of CRC, the recruitment of gene therapy methods seems to be a promising way for the treatment of patients with CRC. Gene therapy is mainly based on the process of gene transfer and gene-editing technologies to replace and correct defective genes. For successful gene therapy, in addition to identification of the target gene, the development of the appropriate delivery system is needed. Viral vectors are one of the most promising methods for gene therapy delivery to colorectal cancer patients. The genomics materials of these viruses can be engineered to successfully express the target genes in infected cells. In addition, viruses simultaneously lyse tumor cells and trigger both humoral and cellular immune responses in the tumor microenvironment. Among the several types of oncolytic viruses, Adenoviruses, a non-enveloped virus with linear double-stranded DNA, have emerged as promising candidates for a gene delivery vehicle and vaccine design due to their high transgene capacity, efficient gene transduction, genetic stability, production at high titer, and ability to infect both dividing and non-dividing cells. In this paper, we will review the results of preclinical and clinical studies to elucidate the efficacy and safety of adenovirus-based gene therapy methods in colorectal cancer patients.
- Methods: We searched PubMed, Google Scholar, and clinicaltrials.gov databases based on appropriate keywords of colorectal cancer, gene therapy, epigenetic, adenovirus, adenoviral vector, CRC patients to identify original articles involving adenoviruses in colorectal cancer gene therapy.
- Results: Several studies preclinically and clinically investigated the therapeutic role of adenoviruses in CRC treatment. For example, Oday Hamid demonstrated the antitumor activity, safety, immune response, and replication of CI-1042 (ONYX-015), an E1B 55-kd gene-deleted replication-selective adenovirus in the CRC patients, proving the efficacy of CI-1042 intravenously to patients with metastatic colorectal cancer. In addition, the tumor-specific apoptotic activity of adenovirus encoding the p53 transgene in colorectal cancer patients was in the phase 1 study of IA. Atencio et al, in 2006. Intratumorally treatment of athymic mice with colon cancer with AdCDUPRT (adenoviral vector encoding the uracil phosphoribosyltransferase) significantly reduced tumor growth rates compared with untreated controls. Adenoviral-mediated transfer of PTEN (Ad-PTEN) suppressed cell divisions and induced apoptosis in CRC.
- Conclusion: Preclinical and clinical studies have demonstrated the safety and preliminary efficacy of adenoviruses in targeting and successful gene therapy of CRC. Hence, Adenovirus mediated gene therapy could be translated to clinic in the future.
- Keywords: Colorectal cancer, Gene therapy, Epigenetic, Adenoviral vector, CRC patients
