Sydney.– The humble yeast has revealed the molecular workings of an anti-cancer drug that stops the growth and spread of tumors in humans by starving their blood supply.  

Until now, University of New South Wales scientists who developed the drug (GSAO) knew that it was lethal against endothelial cells but not why it had any direct impact on tumors themselves.  

The new study reveals that endothelial cells lack the "transport protein" that tumors use to eject foreign molecules that invade their cell structure.  

Endothelial cells are the building blocks of blood vessels. Cancer cells rely on blood vessel growth, known as angiogenesis, to grow and spread to other parts of the body.  

"It's very sexy science," says one the research authors, Professor Philip Hogg, a biochemist with the UNSW Centre for Vascular Research and the Children's Cancer Institute Australia. "We now understand how an anti-cancer drug works in humans thanks to genetic studies using the humble yeast cell."  

Published in today's edition of the prestigious Journal of the National Cancer Institute, the study reveals how researchers "genetically fingerprinted" the transport protein by using genetically modified (mutant) yeast cells. The researchers used 4800 yeast mutants that represent every non-essential gene in the genome.  

"The mutant yeast cells that were vulnerable to the drug lacked the protein that enables them to eject the drug across their cell membrane," says Professor Ian Dawes, a study co-author from the UNSW Ramaciotti Centre for Gene Function Analysis.  

"Yeast cells that lacked the protein died, while those that had the protein didn't," says Dawes. "That told us there was a specific gene encoding a protein that's vital for a cell to protect itself against GSAO."  

Once the researchers knew this they looked for and found a corresponding protein in humans, known as a multi-drug resistance associated protein (MRP).  

"The presence of these transport proteins in tumors is one of the reasons that anti-cancer drugs such as chemotherapy medicines fail against cancer," says Professor Hogg.  

"The reason that GSAO is effective is that it targets tumors indirectly by attacking the endothelial cells that lack this transport protein. So GSAO is lethal against tumors because it chokes the blood supply they rely on to grow and spread."  

The amazing thing is that we've used the humble yeast, which is a less sophisticated cell than a human cell, to reveal the molecular secrets of the drug and how it works in humans.  

GSAO (glutathionarsenoxide) is an angiogenesis inhibitor drug that "starves" tumor cells by stopping them from making blood vessels –known as angiogenesis– that tumors rely on to grow and spread. Professor Philip Hogg and Dr Neil Donoghue from the University of New South Wales invented GSAO in 1999.  

Because all solid tumors of children and adults, such as cancer of the breast, prostate, colon, lung and brain rely on angiogenesis, a single anti-angiogenic drug should be effective against all tumor types.  

This is in contrast to chemotherapy drugs and radiotherapy that are often effective only against certain tumor types. Also, because GSAO is not a conventional "cytotoxic" drug that poisons cancer cells, it does not cause unpleasant side effects such as nausea and hair loss.