Scientists at Yale School of Medicine design a virus to treat ovarian cancer

Marisa Peryer, Senior Photographer

A new Yale study showed that certain genetically modified viruses can cure ovarian cancer in mice. It may be of use in the treatment of ovarian cancer in humans.

Researchers at the Yale School of Medicine have tested a chimeric virus — containing genes from two different viruses — that can selectively infect and kill ovarian cancer cells in mice. Their findings represent a potential breakthrough in the long-term treatment of ovarian cancer in humans. The study was published in the journal Virology on Nov. 12, two weeks after the death of the paper’s lead author Anthony Van den Pol, former professor of neurosurgery and psychiatry at Yale.

“Every year, around 20,000 women are diagnosed with ovarian cancer, which is a smaller number compared to cancer types such as breast cancer,” said Gil Mor, the scientific director of the C.S. Mott Center for Human Growth and Development at Wayne State University and a co-author of the paper. “However, unfortunately only around 4,000 of those women can survive the disease.”

The main reason behind the lethality of ovarian cancer is the lack of treatments preventing the recurrence of the disease. In 80 percent of cases, patients who respond positively to chemotherapy still experience a return of the disease, according to Mor. He explained that once the cancer comes back and begins to spread, there is little that doctors can do.

The inspiration for the study was born out of a collaboration between Van den Pol and Mor many years ago, when they worked in adjacent labs at the Yale School of Medicine. Van den Pol, a research scientist in the Neurosurgery Department, had concentrated his research on the long-term treatment of brain tumors. Mor, on the other hand, had been working on treatments for ovarian cancer. The two scientists decided to collaborate to find an alternative treatment for ovarian cancer through oncolytic viruses, which selectively infect and kill cancer cells.

In the experiment’s in vitro phase, in which the research takes place in laboratory tubes or petri dishes without a living component, researchers made a virus called Lassa-VSV in the laboratory. Lassa-VSV consists of three parts: the Lassa virus, the vesicular stomatitis virus, or VSV, and a fluorescent label to facilitate tracing, according to Nazli Albayrak, a scientist who was involved in the in vitro phase. During this phase, the team infected different ovarian cancer cell lines, eventually choosing the ones that were infected most frequently to proceed with the research. 

Then, after deciding on the cell line, the team injected tumor cells into the bodies of the mice, the paper explains. As the tumor cells began to replicate, the team then injected the Lassa-VSV virus into the tumor clusters. They observed that the virus infected the tumor cells very effectively yet did not harm the healthy cells

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New Technologies Aim to Improve Ovarian Cancer Detection

Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.



Dr Rebecca Stone

To better understand these developments, Medscape recently reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University School of Medicine, in Baltimore, Maryland. This interview has been edited for length and clarity.

Medscape: There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?

Dr Stone: The number of new cases in the United States has actually been declining over the past two decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.

What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?

The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.

p53 gene mutations are thought to occur early in the evolution of ovarian cancer. There are data indicating that these mutations actually occur in cells lining the fallopian tubes. Polymerase chain reaction–based DNA/gene sequencing performed on cervical fluid collected by Pap smears could detect these p53-mutated cells shed from the fallopian tubes.

A strength of this study is that it included healthy controls. None of their Pap smears screened positive for the p53 mutations, unlike the Pap smears of women predating their diagnosis of ovarian cancer.

Limitations of the study include the fact that it had a small sample size. Findings will need to be confirmed in a larger patient population.

Also, the study only looked for p53 gene mutations. Ovarian cancers, like other cancers, are largely thought to occur when there is a buildup of mutations in critical genes that result in uncontrolled cell growth and division. These genetic changes/mutations are acquired during a person’s lifetime. Thus, there are likely early genetic changes/mutations that occur

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