View and review on viral oncology research

Abstract

To date, almost one and a half million cases of cancer are diagnosed every year in the US and nearly 560,000 Americans are expected to die of cancer in the current year, more than 1,500 people a day (data from the American Cancer Society at http://www.cancer.org/). According to the World Health Organization (WHO), roughly 20% of all cancers worldwide results from chronic infections; in particular, up to 15% of human cancers is characterized by a viral aetiology with higher incidence in Developing Countries. The link between viruses and cancer was one of the pivotal discoveries in cancer research during the past Century. Indeed, the infectious nature of specific tumors has important implications in terms of their prevention, diagnosis, and therapy. In the 21st Century, the research on viral oncology field continues to be vigorous, with new significant and original studies on viral oncogenesis and translational research from basic virology to treatment of cancer. This review will cover different viral oncology aspects, starting from the history of viral oncology and moving to the peculiar features of oncogenic RNA and DNA viruses, with a special focus on human pathogens.

Figure 1

(A) Representative* list of cellular/viral protein interactions involved in RNA virus-related oncogenic transformation; (B) Schematic representation of Tax and HBZ roles in HTLV-1 mediated oncogenesis. Tax modulates the expression of many viral and cellular genes and it also promotes malignant transformation through disruption of different host-cell growth control pathways, resulting in aberrant cell division. Moreover, Tax adversely influences cellular homeostasis through a number of mechanisms, including the physical interaction with cell-cycle regulators and transcriptional activation of cell-cycle control genes, leading to uncontrolled cell division and proliferation. The basic leucine zipper protein (HBZ) is encoded by the complementary strand of the HTLV-1 genome, and it is expressed in all ATL cells, where it is capable of promoting cell proliferation and suppressing Tax-mediated transactivation. LTR: Long Terminal Repeat; NFκB: Nuclear Factor kappa-light-chain-enhancer of activated B cells; MHC-I: Major Histocompatibility Complex Class-I; STAT-5: Signal Transducer and Activator of Transcription-5; hTERT: human Telomerase Reverse Transcriptase. *Additional cellular/viral interactions involved in cell transformation and oncogenetic mechanisms have been described. This list is representative, not exhaustive.

Figure 2

(A) Representative* list of cellular/viral protein interactions involved in DNA virus-related oncogenic transformation; (B) p53 and Rb are central targets of viral oncoproteins. The viral proteins Large T antigen of SV40, E1A/E1B of Adenovirus, and E6/E7 of HPV, are capable of interfering with either Rb and/or p53, altering their activities and thus essential cell cycle check-points. PP2A: Protein Phosphatase 2A; TRAFs:Tumor necrosis Factor Associated. * Additional cellular/viral interactions involved in cell transformation and oncogenetic mechanisms have been described.