Well-known antifungal drug shows promise against cancer
Thiabendazole, an antifungal agent in clinical use for 40 years, has recently been shown to inhibit angiogenesis and disassemble newly established blood vessel, and to slow tumor growth and reduce vascular density in preclinical fibrosarcoma tumors.
In mouse studies, thiabendazole reduced blood vessel growth in fibrosarcoma tumors by more than half. As cancers of the connective tissue, fibrosarcomas are generally heavily vascularized with blood vessels, according to a statement from The University of Texas (UT) at Austin, where Edward M. Marcotte and other authors of the PLOS Biology report work as scientists.
Marcotte and colleagues focused on certain genes that they previously discovered were present in both yeasts and in vertebrates. In yeasts, which have no blood vessels, the genes are responsible for responding to various stresses to the cells. In vertebrates, the genes regulate vein and artery growth.
“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,” explained Marcotte in the UT statement.
The group found that thiabendazole inhibited the action of those yeast genes. Further research involving frog embryos that were grown in water with the drug revealed that the embryos either didn't grow blood vessels, or grew blood vessels that thiabendazole dissolved. Once thiabendazole was removed from the water, the embryos' blood vessels grew back.
When the testing moved on to human blood vessel cells, the antifungal was seen to inhibit the growth of these cells. Finally, in the mouse model of fibrosarcoma tumors, thiabendazole reduced blood vessel growth in the tumor and slowed tumor growth.
Marcotte's team now plans to test thiabendazole in clinical trials with humans. “Because new agents that target the vasculature would increase our arsenal for battling cancers resistant to current therapies, there is a clear clinical need for novel approaches to their identification,” wrote the investigators, noting that with thiabendazole already FDA-approved for the treatment of certain infections in humans, the drug is an excellent candidate for rapid translation to the clinic.