Researchers find improved method for treating rare, aggressive, pregnancy-related cancer

Scientists led by Olena Taratula, a nanomedicine researcher at Oregon State University, have found a way to better ensure the drug used to combat the disease reaches tumor cells without damaging healthy tissue.

Findings of the study into choriocarcinoma, which occurs in the United States at a rate of about four cases per 100,000 pregnancies, were published in Small Science.

Typically starting in the uterus, choriocarcinoma develops from cells that were part of the placenta. It can occur after a miscarriage, abortion or ectopic pregnancy, one in which a fertilized egg implants somewhere other than the lining of the uterus.

It can also happen following a molar pregnancy (no embryo forms, and the placental tissue grows abnormally) and even after a full-term pregnancy.

Taratula and collaborators including OSU postdoctoral researcher Babak Mamnoon and Maureen Baldwin, a physician at Oregon Health & Science University, designed a type of drug nanocarrier known as a polymersome to specifically target a protein in choriocarcinoma cells.

Polymersomes are hollow spheres that are synthetic versions of liposomes, lipid-based sacs found in all living cells. The protein the researchers aimed for is equilibrative nucleoside transporter 1, usually abbreviated as ENT-1, which is important for a range of cellular processes, among them DNA and RNA synthesis.

In addition to being abundant in choriocarcinoma cells, ENT-1 is found in the brain, heart, liver and other tissues in the body.

Mamnoon led the research team in mouse model testing that confirmed attaching guanosine, a building block of RNA, to the polymersome allowed it to deliver more of the chemotherapy drug methotrexate directly to tumor cells.

“Given MTX’s role as the mainstay treatment for choriocarcinoma, the critical goal now is to enhance its effectiveness, including faster response times, while simultaneously minimizing side effects,” said Taratula, an associate professor in the OSU College of Pharmacy.

Methotrexate or MTX, a common cancer drug, works by interfering with cells’ ability to use folic acid, essential for making DNA and RNA. By blocking a certain enzyme, MTX thwarts replication of the otherwise rapidly dividing cancer cells.

Common symptoms of choriocarcinoma are pelvic pain and irregular vaginal bleeding. The cancer can quickly spread via the bloodstream to other parts of the body including bones, gastrointestinal tract, breasts, kidneys, liver, lungs, lymph nodes and brain.

“Because choriocarcinoma occurs in people who were recently pregnant, they often have young families, so we need to make getting diagnosis and treatment easier and faster for them,” said Baldwin, an obstetrician/gynecologist at OHSU.

Most cases, especially if caught early, are curable, with a five-year survival rate of about 87%.

“But MTX has poor tumor specificity in standard applications and can cause side effects such as liver and kidney toxicity,” Taratula said. “That’s why we need a specially designed nanoplatform that ensures precise drug delivery and release directly into tumors.”

In the mouse model, the approach reduced tumor size by 95%, working roughly six times better than non-targeted drug carriers. The upshot is more effective treatment coupled with fewer or less severe side effects, and with further research, the same approach could be applied to treating other cancers, Taratula said.

Financial support for the study came from the OSU College of Pharmacy, the OHSU School of Medicine, the National Institutes of Health, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Collaborators included Oregon State’s Ana Paula Mesquita Souza, Tetiana Korzun, K. Shitaljit Sharma, Oleh Taratula, Yoon Tae Goo, Prem Singh, Vladislav Grigoriev and Aryan Lakhanpal.