Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Common antifungal drug decreases tumor growth and shows promise as cancer therapy

21.08.2012
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.

She then tested the drug in developing frog embryos. These are fast growing vertebrates in which scientists can watch blood vessel growth in living animals.

Cha found that frog embryos grown in water with the drug either didn't grow blood vessels or grew blood vessels that were then dissolved away by the drug. Interestingly, when the drug was removed, the embryos' blood vessels grew back.

Cha then tested the drug on human blood vessel cells growing in Petri dishes, finding that the drug also inhibited their growth. Finally, she tested the drug on fibrosarcoma tumors in mice and found that it reduced blood vessel growth in the tumors as well as slowed the tumors' growth.

"We didn't set out to find a vascular disrupting agent, but that's where we ended up," said Wallingford, associate professor of developmental biology and Cha's graduate advisor with Marcotte. "This is an exciting example of the power of curiosity-driven research and the insights that can come from blending disciplines in biology."

The scientists' goal is now to move the drug into clinical trials with humans. They are talking with clinical oncologists about next steps.

"We hope the clinical trials will be easier because it is already approved by the FDA for human use," said Marcotte.

Funding for this research came from the Cancer Prevention Research Institute of Texas (CPRIT), the Welch Foundation, the National Institutes of Health (grant numbers GM067779 and GM088624) and the Howard Hughes Medical Institute (HHMI). Marcotte is the Mr. and Mrs. Corbin J. Robertson, Sr. Regents Chair in Molecular Biology. Wallingford is an HHMI Early Career Scientist.

Additional contacts: Edward Marcotte, professor, 512-471-5435, marcotte@icmb.utexas.edu; John Wallingford, professor, 512-232-2784; wallingford@mail.utexas.edu

Lee Clippard | EurekAlert!
Further information:
http://www.utexas.edu

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Switched-on DNA

20.02.2017 | Materials Sciences

Second cause of hidden hearing loss identified

20.02.2017 | Health and Medicine

Prospect for more effective treatment of nerve pain

20.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>