Cell No. 5 Interpretation of a cancer cell, provided by Angela Canada Hopkins, daughter of a cancer patient.

Cell No. 5 Interpretation of a cancer cell, provided by Angela Canada Hopkins, daughter of a cancer patient.

Viruses and Cancer

The association of viruses and cancer has been known for decades. For human papilloma virus (HPV), there are now effective vaccines that reduce probability of certain cancers. For other cancer-associated viruses, progress has been disappointing. As shown here, the Epstein Barr virus (EBV) – the first human virus to be associated with cancer - enters periods of latency during which most viral genes are not expressed. In some stages, no viral proteins are expressed on the cell surface, making it difficult to develop broadly effective immunotherapies. Despite knowing of EBV’s association with cancer for over half a century, attempts to develop vaccines have not proven successful.

Variability in viral gene expression makes development of broadly effective immunotherapies difficult.

EBV Life Cycle & Latency

Viruses can play multiple roles in cancer. This graphic shows some of the roles EBV plays in one of the many cancers in which it can play varying roles.

Effects on multiple oncogenic & immune avoidance mechanisms problematic for molecularly targeted drug approaches.

EBV Oncogenic Signaling in Nasopharyngeal Carcinoma

Emerging Biomarkers in Head and Neck Cancer in Era of Genomics; Kang, Kiess & Chung, Nature Reviews Clinical Oncology 12, 11-25, 2015.

Viral gene products can drive aberrant cell proliferation, inhibit programmed cell death and other mechanisms that promote formation of cancer. Viruses and cancers have also evolved mechanisms to evade immune detection by up-regulating immunosuppressive signals. Due to these pleiotropic effects, so-called molecularly targeted approaches that target only one role have shown limited ability to impact these cancers.

Epigenetic Re-Programming

Epigenetics refers to mechanisms that control which genes or gene programs are turned on or off. Chemical modification of gene promoter regions via methylation, or acetylation or deacetylation of histones around which DNA is coiled, are major mechanisms by which gene expression is controlled. Epigenetic re-programming has evolved as a means to provide viruses, or cancer cells that harbor them, a survival advantage by down-regulating genes associated with drug effects and suppressing immune response to the virus or host cell.