Oncoviruses: An overview of oncogenic and oncolytic viruses
Contributed to www.dentistchannel.online by Shubhangi Mhaske, Monal Yuwanati, Nikita Bhatnagar. We thank them for sharing the article and enlightening the audience on oncogenic and oncolytic viruses.
Previously Published at the Oncobiology and Targets – Vol 2 | Issue 1 | Jan-Feb 2015
Here’s the abstract, Introduction & Future Prospects from the article. To Read the Complete article press on the link below
Abstract:
The knowledge of tumor biology has created the potential to develop and understand the mystery of the oncogenic and oncolytic viruses. The facts with viral oncogenesis have surprised the mankind by the development of oncolytic therapy by the viruses themselves. The objective of this paper was to overview the concept of oncogenesis and oncolysis by the deoxyribonucleic acid and ribonucleic acid viruses. In spite of the fact that viruses indulge in causing cancers, advances are also being made in the field of oncolysis by viral therapy. Although in its infancy, oncolytic viral therapy has already produced some notable successes. The viruses are selectively modified with incorporation and deletion of genes required for them to be tumor‑specific. These modified oncolytic viruses are also used in oncolysis of oral cancers by administrating them either intratumorally or systemically. With diverse nature of tumors, some being radio‑resistant and another chemo‑resistant, the notion of oncolytic viruses being used as adjunct to the conventional treatment modalities is of great significant value. This paper presents an overview of the various aspects of oncogenic and oncolytic viruses in a concise manner with discussion about the mode of administration of oncolytic viruses, their scope and their future potential in treatment of oral cancers.
Introduction:
Oncogenic viruses the concept of cancer etiology seems to be incomplete without mentioning the indispensable role of viruses. There were 10.9 million new cases, 6.7 million deaths, and 24.6 million persons alive with cancer (within 3 years of diagnosis). As estimated, 15% of all human cancers worldwide may be attributed to viruses, expressing a significant cancer burden worldwide. Much of what is known today about cancer and its related genes responsible for cancer causation can be attributed to the studies on oncogenic deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) viruses. Epstein‑Barr virus (EBV), Human Papillomavirus (HPV), hepatitis B virus, and human herpesvirus‑8are the documented DNA viruses contributing to the carcinogenesis. Human T lymphotropic virus type I (HTLV type I) and hepatitis C viruses (HCV) are the RNA viruses that are considered to be oncogenic viruses (OV). The OV are enlisted in Table 1 with their tumor‑specific types. The various milestones in the discovery of various OV have been enlisted in Table 2.
Viruses being obligatory intracellular parasites encode proteins that reprogram host cellular signalling pathways. This in turn controls the proliferation and differentiation of cells, cell death, integrity of the genome and also recognition by immune system. These processes are governed by complex regulatory network and are surveyed by mechanisms that certify that abnormal cells are removed from the proliferative pool. OV inactivate these surveillance mechanisms that would normally recognize and put out such abnormal cells. Viruses are accepted as causative factor for human cancer. Different guidelines had been proposed to aid in establishing a causal relationship between viruses and cancers. Although few of the guidelines are not applicable for all viruses, still they are quite useful.
Mechanism of Viral Oncogenesis– The characteristic feature of cancer cell is loss of growth control by escaping the checkpoint during normal cell cycle. The retinoblastoma (Rb gene) and p53 genes are main tumor suppressor genes involved in checkpoints. Rb gene acts as an ON‑OFF switch for the cell cycle. This gene brings about its action by forming tight inactive complex with the transcriptional factor (E2F) which is thus not available for progression of cell cycle. The main role of p53 in a normal cell cycle is of surveillance and triggering check point controls that slow down or stops the cell cycle. It mediated its action by transcriptional activation of p21 (member of Cip/Kip family along with p27 and p57) at the G1/S checkpoint of the normal cell cycle. Alteration in these normal pathways by OV (which act as initiators) may lead to uncontrolled proliferation of the tumor. cells. This transformation of the normal cells into cancer cells usually occurs with two distinct phases of Initiation and Promotion. The tumor suppressor genes encode proteins that restrain cell growth and are part of the negative control of cell cycle regulation. The mutation in these genes primarily leads to the uncontrolled proliferation of the cells. The Rb gene encodes a 928‑amino acid phosphoprotein, Rb which is phosphorylated by cyclin‑dependent kinase. This phosphorylation leads to the release of binded E2F and permits the G1 to S transition and thus the replication occurs. In case of p53 gene, there is expression of protein (p21) that inhibits the cdc2 kinase. This basically prevents the premature entry of the cell into the S phase of cell cycle. However, if the cell lacks the functional p53 protein due to damage of wild type of p53 gene, there may be progress toward the transformation of the cell.The mutated genes are now referred to as oncogenes those codes for a protein that can potentially transform normal cell into malignant cell if these oncogenes are transmitted by viruses they are called as viral oncogenes.
Various viruses mainly responsible for the development of oral cancers with their mechanisms of tumorigenesis have been described. These mechanisms vary for both DNA and RNA viruses.
Future Prospects
Oncolytic virotherapy has good future as recent experimental findings have increased hope in research community about utilization of virus as anti‑tumors agent with combination adjunct to the conventional treatment modalities such as chemotherapy and radiotherapy or to replace them in future. Thought lots work still need to be done in this field, recent approval of tumor vaccine and oncolytic viruses by FDA and Chinese SFDA has taken giant step toward bring it in clinical application. There is a long and growing list of new or improved versions of oncolytic viruses. With emergence new technology and understanding of OV and their role in the development of cancer, current obstacles in the development and full utilization of oncolytic viruses can be solved.
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