A large proportion of human cancers have been found to be associated with viruses, including human papilloma virus, Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) and hepatitis viruses. EBV is associated with many cancers of the immune system, known as lymphomas. For example, EBV is found in the tumor cells in many patients with non-Hodgkin's lymphoma, especially in the setting of immunodeficiencies caused by HIV or immunosuppressive drugs used in the transplant setting. With the recent onset of HIV infections and the increased use of transplantation, the incidence of EBV-related lymphoid malignancies has increased over the past few decades. In addition, certain other types of non-Hodgkin's lymphomas derived from T cells and natural killer cells are often characterized by EBV-infected tumor cells. Finally, about one half of Hodgkins lymphoma patients also have EBV present in their tumor cells.
Lymphoid malignancies associated with EBV have a poor prognosis. This includes Hodgkins lymphoma and all varieties of non-Hodgkins lymphoma. Standard therapies are much less effective in patients with EBV-related tumors than in patients who have similar cancers that are not infected with EBV. This has led to experimental therapies that target EBV. Most of these strategies have tried to use the immune system to target and destroy the virus and thus the tumor. These experimental immunotherapeutic approaches have included complicated cell-based therapies. Although effective in some patients, cell-based therapies are complex and expensive procedures that make them impractical for widespread use. Viral vaccines are still in their infancy and have not yet been tested beyond the laboratory.
EBV is also associated with certain solid tumors, including stomach cancer and nasopharyngeal carcinoma. Stomach cancer is the second leading cause of cancer deaths worldwide. About 10-15% of stomach cancers are associated with EBV, which carry a poor prognosis. EBV is found in nearly all nasopharyngeal carcinoma, which is the second leading cause of cancer in China. The disease responds poorly to standard therapy once the disease has spread, which occurs in up to half of patients.
There are a variety of other viruses that cause non-malignant illnesses in which the virus is present in a latent state, but can cause illness when these viruses are reexpressed. Similar to EBV, many of these viruses are members of the herpes virus family, including CMV, Herpes simplex and varicella (the cause of shingles), all of which have viral thymidine kinase. The same approach used to treat EBV could prove useful for treating these viral infections. Another virus, HIV, is present in infected patients in a latent state that cannot be eradicated because it remains hidden in the patient’s genome. The ability to induce expression of viral proteins, combined with standard anti-viral therapy, which targets some of these proteins, has the potential to attack these hidden reservoirs of infection that currently make it impossible to eradicate HIV in infected patients.
