Can Targeted Drugs Developed from the Study of Human Endogenous Retrovirus K Replace Traditional Chemotherapy in terms of Colorectal Tumors?
DOI:
https://doi.org/10.61173/27xe3f16Keywords:
Human Endogenous retrovirus type-K (HERV-K), Colorectal cancer (CRC), Chemotherapy, Active immunity, Monoclonal antibodies, Clustered Reg-ulatory Interspaced Short Palindromic Repeats (CRISPR), Taxane, Topoisomerase inhibitors, Cisplatin, Carcinogen-ic transcripts of HERV-KAbstract
Cancer remains a leading cause of death worldwide, with colorectal cancer (CRC) being one of the most prevalent forms. Traditional chemotherapy, while effective, often comes with significant side effects and limitations, prompting the need for more targeted and less toxic therapeutic strategies. This dissertation explores the potential of Human Endogenous Retrovirus K (HERV-K) as a novel target for cancer treatment, particularly in CRC. HERV-K, a retroviral element embedded in the human genome, has been linked to various cancers due to its reactivation in malignant tissues. The study reviews existing literature on HERV-K's role in carcinogenesis, its protein expression in tumors, and the development of therapeutic strategies targeting HERV-K, such as CRISPR-based gene editing, immune activation, and autoantibody therapies. These emerging strategies are compared with traditional chemotherapy in terms of efficacy, side-effect profiles, and economic feasibility. While HERV-K-based therapies show promise due to their precise targeting and potential for long-term immune protection, they are still in early stages of development and face challenges such as high costs and limited clinical trials. The dissertation concludes that HERV-K-targeted therapies, while promising, cannot currently replace traditional chemotherapy due to certain limitations. Future research should focus on expanding the understanding of HERV-K's role in different cancers and optimizing these therapies for broader application.
References
[1] Di Francia, R., Crisci, S., De Monaco, A., Cafiero, C., Re, A., Iaccarino, G., De Filippi, R., Frigeri, F., Corazzelli, G., Micera, A. and Pinto, A., 2021. Response and Toxicity to Cytarabine Therapy in Leukemia and Lymphoma: From Dose Puzzle to Pharmacogenomic Biomarkers. Cancers, 13(5), p. 966. Available at: https://doi.org/10.3390/cancers13050966.
[2] Drugs.com (2024) Trogarzo (ibalizumab) Prices and Coupons. Available at: https://www.drugs.com/price-guide/ trogarzo (Accessed: 12 May 2025).
[3] Fuchs, N., Kraft, M., Tondera, C., Hanschmann, K., Löwer, J., & Löwer, R. (2011). Expression of the Human Endogenous Retrovirus (HERV) Group HML-2/HERV-K Does Not Depend on Canonical Promoter Elements but Is Regulated by Transcription Factors Sp1 and Sp3. Journal of Virology, 85, 3436-3448. https://doi.org/10.1128/JVI.02539-10
[4] Gong, Q., Li, M., Zheng, S., Wu, Z., Wang, P., Zhang, X., Liang, Y., Qian, W., & Xu, R. (2024). Natural monoclonal autoantibodies against HERV-KI02 Envelope-TM from SLE patients selectively eliminate autoreactive immune cells and cancer cells. bioRxiv. https://doi.org/10.1101/2024.12.14.628522
[5] Grandi, N., & Tramontano, E. (2018). HERV Envelope Proteins: Physiological Role and Pathogenic Potential in Cancer and Autoimmunity.
[6] Ibba, G., Piu, C., Uleri, E., Serra, C., & Dolei, A. (2018). Disruption by SaCas9 endonuclease of HERV-K Env, a retroviral gene with oncogenic and neuropathogenic potential, inhibits molecules involved in cancer and amyotrophic lateral sclerosis. Viruses, 10, 412.
[7] International Human Genome Sequencing Consortium (IHGSC). (2001). Initial sequencing and analysis of the human genome. Nature, 409, 860-921.
[8] Jang, J., Kim, D. and Kim, N., 2023. Recent Developments in Combination Chemotherapy for Colorectal and Breast Cancers with Topoisomerase Inhibitors. International Journal of Molecular Sciences, 24. Available at: https://doi.org/10.3390/ ijms24098457.
[9] Karimi, A., Sheervalilou, R., & Kahroba, H. (2019). A new insight on activation of human endogenous retroviruses (HERVs) in malignant melanoma upon exposure to CuSO4. Biological Trace Element Research, 191, 70–74.
[10] Kraus, B., Fischer, K., Büchner, S.M., Wels, W.S., Löwer, R., Sliva, K., et al. (2013). Vaccination directed against the human endogenous retrovirus-K envelope protein inhibits tumor growth in a murine model system. PLoS One, 8(8), 1–8. doi:10.1371/ journal.pone.0072756
[11] Kraus, B., Fischer, K., Sliva, K., & Schnierle, B.S. (2014). Vaccination directed against the human endogenous retrovirus-K (HERV-K) gag protein slows HERV-K gag expressing cell growth in a murine model system. Virology Journal, 11, 58. https://doi.org/10.1186/1743-422X-11-58
[12] Krens, S.D., McLeod, H.L. and Hertz, D.L., 2013. Pharmacogenetics, enzyme probes and therapeutic drug monitoring as potential tools for individualizing taxane therapy. Pharmacogenomics, 14(7), pp. 555-574. Available at: https://doi. org/10.2217/pgs.13.33.
[13] Krumbhaar, E.B., & Krumbhaar, H.D. (1919). The blood and bone marrow in yellow cross gas (Mustard gas) poisoning: Changes produced in the bone marrow of fatal cases. Journal of Medical Research, 40(3), 497–508.
[14] Muley, H., Fadó, R., Rodríguez-Rodríguez, R. and Casals, N., 2020. Drug uptake-based chemoresistance in breast cancer treatment. Biochemical Pharmacology, 177, p. 113959. doi: 10.1016/j.bcp.2020.113959.
[15] Müller, M., Holst, P., & Nielsen, K. (2022). A Systematic Review of Expression and Immunogenicity of Human Endogenous Retroviral Proteins in Cancer and Discussion of Therapeutic Approaches. International Journal of Molecular Sciences, 23. https://doi.org/10.3390/ijms23031330
[16] NHSA (2024) National Drug Reimbursement List. Beijing: National Healthcare Security Administration. Dean&Francis ISSN 2959-409X
[17] Petropoulos, C. (1997). Retroviral Taxonomy, Protein Structures, Sequences, and Genetic Maps. Cold Spring Harbor: Cold Spring Harbor, NY, USA.
[18] Posso-Osorio, I., Tobón, G. J., & Cañas, C. A. (2021). Human endogenous retroviruses (HERV) and non-HERV viruses incorporated into the human genome and their role in the development of autoimmune diseases. Journal of Translational Autoimmunity, 4, 100137. https://doi.org/10.1016/ j.jtauto.2021.100137
[19] Ragonnaud, E., Neukirch, L., Pedersen, I., Daradoumis, J., Grunddal, K., Duvnjak, L., Bermejo, A., Schroedel, S., Thirion, C., et al. (2022). P03.03 Active immunization against human endogenous retrovirus type K (HERV-K) as an immunotherapeutic strategy against solid tumors. J. Immunother. Cancer, 10, A17.2-A18. [CrossRef]
[20] Reyhanoglu, G. and Smith, T., 2024. Irinotecan. In: StatPearls [Internet]. StatPearls Publishing. Available from: https://www.ncbi.nlm.nih.gov/books/NBK554441/.
[21] Springer (2024) AdisInsight Drug Profile: AVA-001. Available at: (https://adisinsight.springer.com/drugs/800055323) (Accessed: 12 May 2025).
[22] Sawicki, T., Ruszkowska, M., Danielewicz, A., Niedźwiedzka, E., Arłukowicz, T., & Przybyłowicz, K. (2021) A Review of Colorectal Cancer in Terms of Epidemiology, Risk Factors, Development, Symptoms and Diagnosis. Cancers, 13. Available at: https://doi.org/10.3390/cancers13092025.
[23] Siegel, R.L., Giaquinto, A.N., & Jemal, A. (2024) Cancer statistics, 2024. CA: a cancer journal for clinicians, 74(1), pp. 12–49. Available at: https://doi.org/10.3322/caac.21820.
[24] Siegel, R.L., Miller, K.D. and Jemal, A., 2020. Cancer statistics, 2020. CA: a cancer journal for clinicians, 70(1), pp. 7–30. Available at: https://doi.org/10.3322/caac.21590.
[25] Siegel, R.L., Miller, K.D., Fuchs, H.E., & Jemal, A. (2022) Cancer statistics, 2022. CA: a cancer journal for clinicians, 72(1), pp. 7–33. Available at: https://doi.org/10.3322/caac.21708.
[26] Siegel, R.L., Miller, K.D., Wagle, N.S., & Jemal, A. (2023) Cancer statistics, 2023. CA: a cancer journal for clinicians, 73(1), pp. 17–48. Available at: https://doi.org/10.3322/ caac.21763.
[27] Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: a cancer journal for clinicians, 71(3), pp. 209–249. Available at: https://doi.org/10.3322/caac.21660.
[28] Tchounwou, P.B., Dasari, S., Noubissi, F., Ray, P. and Kumar, S., 2021. Advances in Our Understanding of the Molecular Mechanisms of Action of Cisplatin in Cancer Therapy. Journal of Experimental Pharmacology, 13, pp. 303- 328. Available at: https://doi.org/10.2147/JEP.S267383.
[29] Tilsed, C., Fisher, S., Nowak, A., Lake, R., & Lesterhuis, W. (2022). Cancer chemotherapy: insights into cellular and tumor microenvironmental mechanisms of action. Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.960317
[30] Veettil, S., Wong, T., Loo, Y., Playdon, M., Lai, N., Giovannucci, E., & Chaiyakunapruk, N. (2021). Role of Diet in Colorectal Cancer Incidence. JAMA Network Open, 4. https:// doi.org/10.1001/jamanetworkopen.2020.37341
[31] Villesen, P., Aagaard, L., Wiuf, C., & Pedersen, F.S. (2004). Identification of endogenous retroviral reading frames in the human genome. Retrovirology, 1. https://doi.org/10.1186/1742- 4690-1-32
Downloads
Published
Issue
Section
License
Copyright (c) 2025 by the authors.
This work is licensed under a Creative Commons Attribution 4.0 International License.
