Document Type : Review Article
Authors
1
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection Immunity, University of Melbourne, Melbourne, VIC 3000, Australia
3
Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
10.22092/ari.2025.367630.3413
Abstract
Viruses account for around 12 to 20 percent of cancers affecting humans globally, with seven viruses—hepatitis C virus (HCV), hepatitis B virus (HBV), human papillomavirus (HPV), Epstein-Barr virus (EBV), human T-cell leukemia virus type 1 (HTLV-1), Merkel cell polyomavirus (MCPyV), and Kaposi’s sarcoma-associated herpesvirus (KSHV)—being directly implicated in tumorigenesis. These oncoviruses target the Ras/MAPK signaling pathway, which is a pivotal regulator of key cell processes such as growth, differentiation, and programmed cell death. Dysregulated activation of the Ras/MAPK pathway is a major driver in cancer development, progression, and sustenance.
By hijacking this pathway, oncoviruses drive tumorigenesis through mechanisms such as upregulating growth factor receptors, inducing angiogenesis, and promoting invasion and metastasis. They also by downregulating tumor suppressors induce MAPK/ERK pathway, creating a pro-oncogenic environment. For example, HPV infects cells by binding to heparan sulfate proteoglycans and entering via endocytosis. the integration of viral DNA into the host genome leads to the overexpression of E6 and E7 oncoproteins. These proteins degrade tumor suppressors p53 and pRb, respectively, disrupting cellular safeguards and promoting tumorigenesis. Blocking the E6-p53 and E7-pRb complexes could be a promising strategy to suppress viral infections and halt cancer progression. Similarly, in HTLV-1-associated Adult T-cell Leukemia, the Tax1 oncoprotein increases Ras-GTP levels and ERK phosphorylation, promoting an anti-apoptotic state that facilitates viral replication. Targeting this pathway with agents like Ras farnesylcystein mimetics has demonstrated potential in restoring apoptosis sensitivity.
Therefore, understanding these mechanisms provides critical insights into therapeutic targets for virus-associated cancers. Further research into these interactions is essential for developing effective therapies to combat these malignancies.
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