By Mark M. Green
Cancer patients in the 1800s were observed, too often to be chance, to be relieved of their cancerous tumors when they were ill with respiratory problems. When viruses were discovered later in that century, it was hypothesized that viral particles were responsible for the effect on the cancerous tumors. The discovery of viruses arose from the fact that infectious fluids, as from one animal or person or plant to another, remained infectious even after processes were used to kill or remove bacteria. Early after the discovery of viruses, doctors began to experiment with using viruses to treat cancer, but with mixed results. Interestingly, the greatest success came with patients whose immune systems were depressed, which was understood as arising from the fact that the virus, which was therapeutic against cancer, was not removed from the blood of patients by their own immune systems.
In the middle years of the 20th century, doctors tried using viruses as a treatment against cancer with some success, although too often killing the patient from the viral infection. This treatment strategy was therefore pretty much abandoned, returning cancer treatment to radiation and chemotherapy, which constitute most treatments today. An excellent article on the history of “viral therapy” can be found at: http://www.nature.com/mt/journal/v15/n4/full/6300108a.html
However, in recent decades, the ability to alter the genetic material of viruses has given hope for their use to battle cancer, by removing the viral characteristics causing human disease. Nevertheless, major problems remain to be solved in suppressing aspects of the immune systems of patients to allow the therapeutic virus to reach the tumor. Another problem involves delivering the virus to the tumor and the inability to use the virus systemically. Some success does appear within the Food and Drug Administration of the United States and the European Medicines Agency by recommending and allowing the use of a genetically modified virus (T-VEC) to attack certain cancers that, in unmodified form, causes herpes.
One specific example of the effort to move forward on viral therapy for cancer treatment is underway based on work at the University of Calgary, which led to a company called Oncolytics Biotech, located in Calgary. The company’s work is focused on the fact that many metastatic cancers arise from a mutated protein, Ras protein, which is responsible for cell growth. When a type of mutation occurs in this protein, the protein function can be turned on permanently so that cell growth occurs without limit, giving rise to cancerous tumors. A virus commonly encountered in human beings, reovirus, that causes infections that are subclinical, or in other words, give rise to no or very slight symptoms, has been discovered to preferentially infect cells in which the Ras protein is, as it is described, “turned on”. Cell growth, as noted above, is unrestricted. Infection of certain tumors by a reovirus causes the cancerous cells to produce more reoviruses, and causes lysis of the cancerous cell walls, killing the cancerous cells and releasing more of the reovirus, which can then go on to kill more cancerous cells. The work in Calgary is based on this information and cancer therapeutic products based on the reovirus are in progress in trials that could lead to wide use in cancer therapy. In an article written by Heidi Ledford in Nature/News, Brad Thompson of Oncolytics Biotech was interviewed. He described the general idea behind viral therapy for cancer succinctly, by pointing out that cancerous cells in their high growth leading to tumors are far more susceptible to infection than normal cells.
Here is how Brad Thompson expressed the general idea in Ledford’s article: “Malignancy can suppress normal antiviral responses, and sometimes the mutations that drive tumor cells also make cells more susceptible to infection. Viral infection can thus ravage a tumor while leaving healthy cells untouched….”
It appears that the infectious characteristics of viruses may lead to important new medical procedures to deal with cancer.