A Virus Can Treat Cancer?

A chicken-killing virus? To treat cancer?

Ever thought a chicken-killing virus could be used to treat cancer? Probably not. But a recent study has discovered amazing potential in using Newcastle disease virus to kill prostate cancer cells. In what is known as oncolytic virotherapy, viruses like the one used in this recent study are implemented as tools to destroy cancer. Newcastle disease virus (NDV) is an avian paramyxovirus that infects wild and domestic bird species. It can cause flu-like symptoms and mild conjunctivitis in humans, but does not pose a significant threat to us. In addition to NDV being essentially non-pathogenic to humans, it can be used in cancer treatment strategies because it is an inherently tumor selective oncolytic virus. This potentially daunting description essentially translates to NDV’s ability to target and destroy cancer cells without posing a threat to healthy cells. In the recent study by Shobana et al. (2013), the authors investigated this virus’s potential for specifically killing human prostate cancer cells.

Newcastle disease virus

Why is this treatment so important?

Such an investigation has significant clinical implications, given that prostate cancer is the second leading cause of cancer-related deaths in the United States. To put things in perspective, almost 17% of men will develop prostate cancer at some point in their lives. Treatment of prostate cancer typically involves hormone therapy or chemotherapy, both of which have significant adverse side effects. Furthermore, current treatments for hormone-resistant prostate cancer only marginally increase survival and are often aimed at palliative, or pain management, care. Given the adverse effects and low effectiveness of the typical treatment approaches, there is much hope that we can begin to turn to oncolytic virotherapy as a novel approach to prostate cancer treatment. Using NDV as the vector in this therapy would alleviate patients from the often painful side effects of more standard cancer treatments. Although many issues are still associated with oncolytic virotherapy,  Shobana et al. (2013) present findings that make scientists hopeful such a treatment will soon have real clinical applications for treatment of what is now the second leading cause of cancer death in men.

Fighting Fire with Fire

To some it may seem counterintuitive to use an infection to cure a disease. Surprisingly enough, this is exactly what researchers have been doing using oncolytic virus therapy.  Oncolytic viruses are naturally occurring or engineered viruses that selectively target cancer cells by identifying common cancer characteristics such as defective immune responses or abnormalities in cellular signaling pathways. Once viruses infect the cancer cells, they replicate within the cell and eventually kill it.  As such, the infectious qualities of oncolytic viruses are becoming increasingly useful tools during cancer treatment. 

Past studies have shown great potential for oncolytic therapy using vesicular stomatitis virus, (VSV) -- a negative-strand RNA virus that generally infects insects, cattle, horses and pigs (1).  VSV has proven to be particularly conducive to oncolytic virus therapy as a result of its small easily manipulated genome and relative innocuity in humans (2). So far, VSV vectors have been used for immunization against HIV and influenza (2,3).  Additionally, testing has occurred that suggests that there is also potential of VSV as a recombinant cancer vaccine vector (4). 

Despite the high hopes for the use of VSV as oncolytic cancer treatment, a recent 2012 study suggests that human pancreatic ductal adenocarcinoma (PDA) cells do not consistently permit VSV infection (5).  In some cases, PDA cells retained all resistance and were still able to activate functional interferon (IFN) responses. As a result, the study of the interferons – proteins released by host cells to interrupt viral replication – and their association with oncolytic VSV infection is of great interest to researchers.

Measles Vaccine Virus: A New Weapon against Cancer?

When viruses come to mind, most people tend to think of their threats against human health.  However, scientists are rapidly discovering a new branch of medicine: oncolytics.  Oncolytics is the use of viruses to kill cancerous cells, while leaving the surrounding healthy tissue unaffected.  Certain forms of cancer are ideal for oncolytic research, due to their location and lack of viable treatment.  A sarcoma is a certain type of cancer that comes from mesenchymal tissue (1).  Sarcomas can be divided into two categories: soft-tissue or bone (1).  While certain types of surgeries can cure sarcoma, other forms are inoperable, and difficult to treat with surgery, chemotherapy, or radiation (1).  Thus, sarcomas are optimal for experimental oncolytic research.

            In a recent study published by the Journal of Virology, German scientists from the University Hospital Tubingen investigated the effectiveness of the measles vaccine virus (MeV) in treatment of eight types of sarcoma cell lines: HT1080 (human fibrosarcoma), A673 (extraosseous Ewing sarcoma), SRH (sclerosing spindle cell rhabdomyosarcoma), BR and ZF (alveolar rhabdomyosarcoma), SCOS (osteosarcoma), CCS (clear cell sarcoma), and ST (dedifferentiated leiomyosarcoma).  Researchers chose to focus on MeV due to its previous oncolytic potential in several types of cancers, such as ovarian carcinoma (2), lymphoma (3), and glioblastoma (4).  Typically, oncolytic viruses are equipped with “suicide genes,” which can produce localized chemotherapy in an infected cell (5).  In this experiment, the researchers armed MeV with super cytosine deaminase (SCD), which converts 5-fluorocytosine (5-FC) into 5-FU, a type of clinical chemotherapy, thus producing MeV-SCD (6).