Tumor viruses and cancer biology: Modulating signaling pathways for therapeutic intervention

Abstract

Tumor viruses have provided relatively simple genetic systems, that can be manipulated for understanding the molecular mechanisms of the cellular transformation process. A growing body of information in the tumor virology field provides several prospects for rationally targeted therapies. However, further research is needed to better understand the multiple mechanisms utilized by these viruses in cancer progression in order to develop therapeutic strategies. Initially viruses were believed to be associated with cancers as causative agents only in animals. It was almost half a century before the first human tumor virus, Epstein-Barr virus (EBV), was identified in 1964. Subsequently, several human tumor viruses have been identified including Kaposi sarcoma associated herpesvirus (KSHV), human papillomaviruses (HPV), hepatitis B virus (HBV), Hepatitis C virus (HCV), human T lymphotropic virus (HTLV-1) and recently identified Merkel cell polyomavirus (MCPyV). Tumor viruses are sub-categorized as either DNA viruses, which include EBV, KSHV, HPV, HBV and MCPyV or RNA viruses such as HCV and HTLV-1. Tumor-viruses induce oncogenesis through manipulating an array of different cellular pathways. These viruses initiate a series of cellular events, which lead to immortalization and proliferation of the infected cells by disrupting the mitotic checkpoint upon infection of the host cell. This is often accomplished by functional inhibition or proteasomal degradation of many tumor suppressor proteins by virally encoded gene products. The virally infected cells can either be eliminated via cell-mediated apoptosis or persist in a state of chronic infection. Importantly, the chronic persistence of infection by tumor viruses can lead to oncogenesis. This review discusses the major human tumor associated viruses and their ability to modulate numerous cell signaling pathways, which can be targeted for potential therapeutic approaches.

Biology of Human Papillomavirus Infections in Head and Neck Carcinogenesis

“…The HPV types have also been grouped into mucosal or cutaneous types, based on their tropism for specific epithelial sites. Mucosal HPV types found preferentially in precancerous and cancerous lesions have been designated as 'high-risk' types and these include types 16,18,31,33,34,35,39,45,51,52,56,58,59, 66, 68, and 70. Mucosal HPVs found in benign genital warts and other non-malignant lesions are generally labeled as 'low-risk' types, the most important ones being HPV 6,11,42,43, and 44 [1,2].…”

“…The role of HPV in the development of HNSCC includes a coordinated targeting of multiple pathways by HPV oncoproteins E5, E6 and E7 [21,23,36,57,59]. Modeling the molecular circuitry of cancer has been presented by Hahn and Weinberg in 2002 [60].…”

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“…While the nanocarriers could be selected from a polymeric micelle system or inorganic material, nanocapsule could be represented by pillar (n) arenes whose biological supremacy over other macro cycles has been delineated [17]. Furthermore, water soluble form of pillar [6] arenes, namely carboxylated pillar [6] arenes could be functionalized by antigen specific sequence or antibody drug conjugate. Additionally, nanocarriers could be encapsulated with an MRI module, to enable simultaneous tracking and treatment response monitoring.…”

“…While adoptive cell transfer remains the oldest, wherein T cells are isolated from the body and cultured and genetically modified for specificity towards tumour associated antigens (TAAs) and subsequently reintroduced to the patient. A similar approach is undertaken with cancer vaccines, wherein TAAs are indentified and are co-administered to stimulate immune response, sometimes in the context of professional antigen presenting cells (APCs) such as dendritic cells (DCs) [5] or viral vectors as in the case of viral vaccines [6].…”

Tumorigenesis related to retroviral infections

“…Oncogene-bearing retroviruses normally cause tumors with a short latent period, whereas oncogenic retroviruses that lack oncogenes induce tumors with a much longer latent period [4]. The chronic persistence of tumor virus infection can lead to oncogenesis [5].…”