Scientists report on the surprising discovery that a generic drug used for over 40 years as an antifungal agent may also prove to be an effective treatment for cancer. Researchers at the University of Texas at Austin (UTA) have found that the oral antifungal agent thiabendazole acts as a vascular disrupting agent that reduces the growth of both tumor-feeding blood vessels and tumors in experimental mice carrying fibrosarcomas. The investigators are already looking to move the drug into clinical trials in a cancer setting.
Reporting in PLoS Biology, Hey Ji Cha, Ph.D., Edward Marcotte, Ph.D., John Wallingford, and colleagues admit the finding that thiabendazole acts as a vascular disrupting agent was the serendipitous result of some multidisciplinary research. “We didn’t set out to find a vascular disrupting agent, but that’s where we ended up,” states Wallingford, UTA associate professor of developmental biology.
The work was founded on previous studies by the team that had identified genes in yeast that, in vertebrates, are involved in regulating blood vessel development. Yeast has no use for blood vessels, and in these cells the genes appear to play a role in responding to certain types of cellular stress.
“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,” Dr. Marcotte explains. And it was this search that initially identified thiabendazole as an inhibitor of the genes in yeast. Encouragingly, when the drug was then tested in developing frog embryos, it dramatically inhibited blood vessel growth and even caused the destruction of pre-existing blood vessels. When the drug was withdrawn, the blood vessels grew back. Studies in mice then confirmed that thiabendazole had a similar anti-angiogenic effect on tumor blood vessels in cancer-bearing mice, reducing vessel growth by up to 50%.
“This is an exciting example of curiosity-driven research and the insights that can come from blending disciplines in biology,” Dr. Wallingford concludes. The researchers say they hope to progress thiabendazole into clinical trials as an anticancer drug, and are already in discussions with clinical oncologists.