Cancer cells: Domineering on the inside, on the outside I beg for mercy.
Humanity has made progress over several centuries in the search for cancer treatments. Despite chemotherapy and radiotherapy becoming the mainstream methods of treatment, scientists are still exploring new approaches. A recent study attempted to use the Zika virus—a well-known virus—to attack a high mortality human tumor in mice—neuroblastoma. The results showed that the Zika virus almost completely cleared the neuroblastoma transplanted into the mice without any recurrence, and the Zika virus did not cause any adverse effects on the mice.
In fact, using viruses to combat cancer is not a new concept. Even before bacteria and viruses were known to cause diseases, medical records indicated that some infectious diseases could reduce cancer size, most of which were caused by bacterial infections such as diphtheria, malaria, gonorrhea, syphilis, and tuberculosis; as well as some diseases caused by viruses, such as influenza, hepatitis, measles, and smallpox.
This phenomenon is known as the “Saint Peregrine tumor”, which originated from the experience of the 13th-century Italian priest Peregrine Laziosi. He had a tumor in his leg, which completely regressed after developing an infection ahead of a scheduled amputation surgery. Hence, he is revered as the “patron saint of cancer patients”.
In the early 18th century, a French surgeon documented the experience of a breast cancer patient, whose tumor started to disappear after the affected area developed severe inflammation and gangrene. A Bohemian anatomist of the period also reported similarly, after a patient’s tumor began to shrink following a three-day fever from malaria. These cases prompted doctors to attempt treating cancer with bacteria or viruses.
By 1868, a cancer patient experienced a high fever after being infected with the pus-forming Streptococcus pyogenes and subsequently, the tumor was found to have shrunk. This inspired a doctor named William Coley, who began to combine inactivated Streptococcus pyogenes and Serratia marcescens to create the so-called “Coley’s toxins” to treat cancer without causing infection. Although reports claimed that patients had a survival rate exceeding 70% after using Coley’s toxins, later scientists were skeptical of this data, believing Coley’s research to have a small sample size and that results may exhibit selection bias.
Through historical records, we have found an increasing number of cases similar to the “Saint Peregrine tumor.” For example, in 1896, a 42-year-old woman with myelocytic leukemia experienced a significant reduction in the size of her liver and spleen, and a reduction in white blood cell count by more than 70 times, after going through an infection suspected to be the flu.
In another case, a 4-year-old boy suffering from lymphocytic leukemia showed signs of varicella. A few days later, the child’s spleen and liver returned to normal size, white blood cell count normalized, and there was a significant increase in platelets and hemoglobin, indicating a temporary remission of the disease. Although this improvement only lasted a month, the boy’s condition deteriorated again and he eventually passed away.
In the subsequent decades of scientific and technological development, researchers began to gradually understand the principles behind these cases. They found that certain viruses have unique abilities to infect and kill cancer cells specifically, and these viruses are known as “oncolytic viruses.”
Scientists then started to explore the use of different types of oncolytic viruses to fight cancer. For example, in 1949, an experiment showed some symptom relief in Hodgkin’s lymphoma patients after being infected with the hepatitis B virus. In 1952, research confirmed that the West Nile virus could replicate in cancer cells, but the neurotoxicity it caused was a problem that could not be ignored. While these works revealed the potential of viruses to combat cancer, the severe side effects often associated with their use meant they lacked therapeutic safety.
Entering the 1990s, researchers began to attempt using genetic engineering technology to reduce the side effects of oncolytic viruses. In 2005, the first oncolytic virus drug, H101 (Oncorine), was approved for use in China, followed by the approval of several oncolytic virus drugs in countries including the United States and Japan.
Oncolytic viruses may suppress cancer for various reasons. Cancer cells evade immune cell detection by altering interferon signaling pathways, but this also reduces their ability to resist foreign viruses, providing an opportunity for oncolytic viruses to invade. Infection by certain oncolytic viruses can make tumors more recognizable and thus cleared by the human immune system. In addition, some oncolytic viruses can alter the microenvironment around the tumor, making it less conducive to the tumor’s survival.
Similarly today, the Zika virus has shown new promise in the fight against neuroblastoma, the most common malignant tumor diagnosed in infants and accounting for 15% of childhood cancer-related deaths in the United States. Potentially, the use of Zika virus opens a new direction for the treatment of such diseases.
The long-term survival rate for patients with high-risk neuroblastoma has so far remained below 40%. This situation has sparked widespread concern and in-depth research in the scientific community. Since the Zika virus was first identified in Africa, it has been primarily transmitted by mosquito bites, posing a threat to human health. Especially for pregnant women, Zika virus infection can lead to attacks on the embryo’s neural precursor cells, causing congenital defects like microcephaly in children after birth, and sometimes leading to miscarriage. However, for adults, the Zika virus often does not cause significant symptoms and typically presents with mild rash, fever, muscle weakness and recovers quickly.
Interestingly, neural precursor cells are also precisely the main targets attacked by the Zika virus, a discovery that opens new doors for Zika virus’s potential applications in medical science. Latest research reveals the possibility of Zika virus fighting against neuroblastoma. In this study, researchers transplanted human malignant neuroblastoma cells into mice and induced proliferation. They then injected the Zika virus into the tumor region within the mice. What’s remarkable is that the Zika virus induced massive cell death in the cancer cells, and the tumor was almost completely eliminated post-treatment, with no signs of recurrence observed. More importantly, the area affected by the Zika virus seemed to be limited within the tumor cells, with almost no other areas of the mouse body being invaded. In the examined mouse organs, the amount of Zika virus was several orders of magnitude lower than in the tumor region and continued to decrease over time. The test mice exhibited no symptoms associated with Zika virus infection after tumor elimination.
Zika virus’s specificity in clearing cancer cells lies not only in its ability to combat neuroblastoma. In a 2017 in vitro study, the Zika virus attacked human glioblastoma tissues and cultured organoids, successfully inhibiting tumor growth. The application of Zika virus also improved the life expectancy of mice that had human glioblastoma transplanted into them.
Continuing this research, another study in 2018 found more positive results. Mice transplanted with human central nervous system tumors not only had an increase in survival time after receiving Zika virus injections, reduced tumor burden, but also a decrease in cancer cell spread, significantly alleviating the overall condition. Interestingly, West Nile virus, similar to Zika virus, not only attacks cancer cells but also affects healthy neural cells. Further research found that Zika virus mainly attacks cancer cells that express the CD24 protein, which is usually related to the state of cell differentiation, with high expression of CD24 in tumors considered an important factor driving tumor growth, and also an important indicator for predicting poor prognosis in various cancers.
Virus efficacy does not always cause harm; under certain circumstances, they are also seen as potential tools in medical research.
In the field of cancer treatment, scientists are creatively considering the use of viral characteristics to attack cancer cells, and recent studies have shown that Zika virus is becoming a new hope. This virus, commonly associated with congenital microcephaly, was unexpectedly found to selectively attack and eliminate a certain class of cancer stem cells with differentiation capabilities.
Cancer stem cells are the root of malignant tumors, and they are difficult to treat because they are able to self-renew and produce new cancer cells. However, the Zika virus appears to have its own advantages in this battle, as it can locate and kill these tenacious cancer cells.
Interestingly, the Zika virus particularly favors cells that express the CD24 protein, and this protein is precisely a marker on the surface of some cancer stem cells. This means that for other types of tumors that also express the CD24 protein, Zika virus may likewise exert its lethality.
Therefore, scientists are continuously exploring the possibility of using the Zika virus to treat cancer. Imagine if successful, a treatment method based on the Zika virus could bring good news to patients fighting against cancer.
We look forward to the day when this therapy, after thorough research and clinical trials, becomes a part of cancer treatment, truly benefiting human health.
