2007 Media Releases
Friday 16 November, 2007
La Trobe cell death research leads to novel anti-cancer drug
Scientists at La Trobe University have discovered how a new drug that targets proteins that inhibit the normal process of cell death (a process known as apoptosis) kills cancer cells.
The research has important implications for the next generation of cancer treatments and highlights the key mission of the University’s new Australian Institute for Molecular Medicine.
A research team led by Dr John Silke and Professor David Vaux has discovered that a new drug targets a cell death inhibitor protein (cIAP1) and can cure laboratory mice bearing human cell cancers.
The research is a culmination of a decade of basic research into inhibitor of apoptosis proteins (IAPs), which were first found in viruses that infect the cells of caterpillars. The viruses carry genes for IAPs to stop the caterpillar’s cells from killing themselves, giving the viruses more time to replicate.
Professor Vaux’s laboratory showed that these insect viral IAPs can also inhibit the death of human cells. This led the researchers to identify similar IAP genes in mice and humans.
They later discovered an inhibitor of the IAPs – a protein known as ‘Smac’ or ‘Diablo’ – which can effectively neutralise the IAPs, causing the cells die.
As abnormally high levels of IAPs have been found in several types of human cancers, this suggested that cells in these cancers might depend on IAPs for their survival.
Based on this research, TetraLogic Pharmaceuticals, in Pennsylvania USA, produced a drug that mimics Smac to inhibit IAPs in cancer cells. Together with the team at La Trobe, they have now shown that this ‘smac-mimetic’ IAP antagonist drug targets cIAP1, leading to production of a cytokine called Tumor Necrosis Factor that kills the tumour cells.
These latest findings were published today in the prestigious international scientific journal, Cell, along with a another research paper from Genentech Inc., which has independently developed another IAP-antagonist drug, and commenced testing it in Phase I human clinical trials.
Dr Silke says: ‘Although we won’t know if these new drugs will work in humans until the clinical trials have been completed, they illustrate a much more intelligent approach to combating cancer – by identifying the genes that cause cells to become cancerous, and then developing drugs to specifically target those genes to kill the cancer cells.’
Professor Vaux says these results show how investment in basic research – ‘in something as obscure as insect viruses’ – can potentially lead to important new treatments for human diseases. ‘They also reveal the global nature of collaboration in medical research.’
The international scientific teams are headed by John Silke and David Vaux. They include James Vince – lead author of the research paper just published in Cell –Lynn Wong, Nufail Khan, Rebecca Feltham, Afsar Ahmed, Diep Chau, and Bernard Callus (La Trobe University); Chris Benetatos, Sri Chuduru, Steve Condon and Mark McKinlay (TetraLogic Pharmaceuticals, USA); Rob Brink (Garvan Institute, Sydney); Martin Leverkus (Germany) Vinay Tergaonkar (Singapore) Pascal Schneider (Switzerland) and Frank Koentgen (Ozgene).
The research was funded by the Australian National Health and Medical Research Council (NHMRC); the Australian Research Council (ARC); and the US-based Leukemia and Lymphoma Society. Further information:
Contacts
Dr John Silke T: 03 9479 1270: E: j.silke@latrobe.edu.au
Professor David Vaux T: 03 9479 2211 E: d.vaux@latrobe.edu.au
Adrienne Jones (Media and Communications) T: 03 9479 5513 E: adrienne.jones@latrobe.edu.au
Cell paper available (from 4.a.m. November 16) on:
www.cell.com
or embargoed on http://www.eurekalert.org/jrnls/cell/pages/cell.php.
Further background on the following websites:
http://www.latrobe.edu.au/bulletin/archive/1007/news1.htm
http://www.latrobe.edu.au/bulletin/archive/0506/news2.html
The Australian Institute for Molecular Medicine (AIMM) is based at La Trobe University’s main Melbourne campus at Bundoora. It is a partnership between La Trobe University and the Co-operative Research Centre for Biomarker Translation with close links to researchers at The Walter and Eliza Hall Institute and the Co-operative Research Centre for Cancer Therapeutics located on the La Trobe Biosciences Precinct at Bundoora. AIMM plans to build a facility at the University in 2009 dedicated to research into the molecular basis of human diseases.
Professor David Vaux was this year awarded one of the nation’s newest and most prestigious science awards – an Australia Fellowship from the National Health and Medical Research Council valued at $4 million over five years. In the 1980s Professor Vaux discovered the first molecular components of the mechanism involved in the cell death, known as ‘apoptosis’. He is now recognised internationally as a leading researcher in what has become one of the hottest fields of bio-medical science.