During investigations into the relationship between yeast, frogs, mice and humans, researchers from Texas University’s College of Natural Sciences have discovered that an inexpensive antifungal drug called thiabendazole, slows tumor growth and could potentially be used as chemotherapy for cancer treatment. The study was published the PLoS Biology.
Thiabendazole has been used for antifungal treatment for 4 decades. The FDA-approved generic drug that is taken orally is currently not used for the treatment of cancer.
Hye Ji Cha, Edward Marcotte, John Wallingford and their team discovered that thiabendazole is a vascular disrupting agent, since it destroys newly established blood vessels, which could be of significant use as a chemotherapy tool given that inhibiting blood vessels, and vascular, growth is known to starve tumors and tumors prompt the growth of new blood vessels to feed their out-of-control growth.
The team conducted an experiment in mouse models and found that thiabendazole reduced the growth of blood vessels in fibrosarcoma tumors, i.e. cancers of connective tissue that are typically heavily populated with blood vessels by more than 50%. They also observed that the drug decreased the speed in which tumors grow.
Marcotte, professor of chemistry, declared:
“This is very exciting to us, because in a way we stumbled into discovering the first human-approved vascular disrupting agent. Our research suggests that thiabendazole could probably be used clinically in combination with other chemotherapies.”
The discovery is a culmination of research across different disciplines and organisms. Marcotte and his team discovered in a previous study that genes in single-celled yeast and vertebrates share evolutionary history. Whilst the genes in yeasts are responsible for responding to various stresses to the cells, in vertebrates, the genes have been repurposed to regulate vein and artery growth, or angiogenesis.
Marcotte declared: “We reasoned that by analyzing this particular set of genes, we might be able to identify drugs that target the yeast pathway that also act as angiogenesis inhibitors suitable for chemotherapy.”
Their theory was confirmed. Cha, one of the University’s graduate students in cell and molecular biology at the university was looking for a molecule that would block the action of those yeast genes, and discovered that thiabendazole managed to achieve this. Cha subsequently tested the drug in developing frog embryos, as these are fast growing vertebrates that allow scientists to observe the growth of blood vessels in living animals. She discovered that frog embryos grown in water with the thiabendazole either failed to grow blood vessels, or, those that grew were dissolved by the drug. To their surprise, they noted that the embryo’s blood vessels grew back when the drug was removed.
When Cha tested thiabendazole in Petri dishes in which human blood vessel cells were grown, she discovered that the drug also inhibited the growth in the human cells. She then tested the drug on fibrosarcoma tumors in mice, which also confirmed a slow-down of tumor growth and decreased blood vessel growth.
Wallingford, associate professor of developmental biology and Cha’s graduate advisor together with Marcotte, said: “We didn’t set out to find a vascular disrupting agent, but that’s where we ended up. This is an exciting example of the power of curiosity-driven research and the insights that can come from blending disciplines in biology.”
The team is planning to conduct clinical trials with humans and is currently discussing the next steps with clinical oncologists. Marcotte concludes: “We hope the clinical trials will be easier because it is already approved by the FDA for human use.”
Written by Petra Rattue