An inexpensive antifungal drug, thiabendazole, slows tumor growth and shows promise as a chemotherapy for cancer. Scientists in the College of Natural Sciences at The University of Texas at Austin made this discovery by exploiting the evolutionary relatedness of yeast, frogs, mice and humans.
Thiabendazole is an FDA-approved, generic drug taken orally that has been in clinical use for 40 years as an antifungal. It is not currently used for cancer therapy.
Hye Ji Cha, Edward Marcotte, John Wallingford and colleagues found that the drug destroys newly established blood vessels, making it a "vascular disrupting agent." Their research was published in the journal PLOS Biology.
Inhibiting blood vessel, or vascular, growth can be an important chemotherapeutic tool because it starves tumors. Tumors induce new blood vessel formation to feed their out-of-control growth.
In trials using mice, the researchers found that thiabendazole decreased blood vessel growth in fibrosarcoma tumors by more than a half. Fibrosarcomas are cancers of the connective tissue, and they are generally heavily vascularized with blood vessels.
The drug also slowed tumor growth.
"This is very exciting to us, because in a way we stumbled into discovering the first human-approved vascular disrupting agent," said Marcotte, professor of chemistry. "Our research suggests that thiabendazole could probably be used clinically in combination with other chemotherapies."
The scientists' discovery is a culmination of research that crosses disciplines and organisms.
In a previous study, Marcotte and his colleagues found genes in single-celled yeast that are shared with vertebrates by virtue of their shared evolutionary history. In yeasts, which have no blood vessels, the genes 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.
"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," said Marcotte.
Turns out they were right.
Cha, a graduate student in cell and molecular biology at the university, searched for a molecule that would inhibit the action of those yeast genes. She found that thiabendazole did the trick.