Statins could help save Tasmanian devils
Cholesterol-lowering drugs could help delay the spread of the deadly Tasmanian devil facial tumour disease and may help protect the endangered marsupials from extinction, according to new research by Australian and Spanish scientists.
By studying the molecular and metabolic mechanisms that drive devil facial tumour disease (DFTD), the researchers found tumour cells required a minimum amount of cholesterol to multiply. If cholesterol synthesis was drastically reduced, the tumours did not grow.
DFTD is a fatal, very aggressive form of transmissible cancer. It is spread through the transfer of living cancer cells when Tasmanian devils bite each other, and has resulted in an 80% drop in the population of wild Tasmanian devils since the disease first emerged in the mid-1990s. However, the metabolic drivers underlying DFTD have not been thoroughly studied until now.
Research co-leaders Dr Manuel A Fernández-Rojo and Dr Maria Ikonomopoulou, who are now based at the IMDEA Food Institute in Spain, conducted most of the study at the QIMR Berghofer Medical Research Institute. Dr Fernández-Rojo said identifying the impact of manipulating the cholesterol content in DFTD cells led the research team to look at cholesterol-lowering drugs as potential treatments.
“Our laboratory experiments showed devil facial tumour disease cells grew and spread more, using glucose as a source of energy, if they were stimulated with drugs that activated the nuclear receptor LXR (Liver-X-receptor). LXR is involved in regulating cellular cholesterol levels,” Dr Fernández-Rojo said.
“We used this understanding of the biology that drives the disease to examine if statins, which are drugs that inhibit cholesterol synthesis, would stop the tumour cells multiplying.
“We found statins reduced the growth of the devil facial tumours in the laboratory and we believe more research should now be undertaken to see whether these cholesterol-lowering drugs could be used to inhibit, or at least slow, the growth of DFTD and hopefully help protect the species.”
Dr Ikonomopoulou said the research findings, published in the journal Cell Reports, might also have implications for malignant and highly aggressive cancers in humans.
“We know statins work on tumour cells in lab experiments, so we now want to expand our study of the drugs in stopping the spread of cancer tumours,” Dr Ikonomopoulou said.
“Human cancer cells undergo similar metabolic adaptation to grow as those exhibited by DFTD cells in our research.
“This raises the question of whether statins, which are currently prescribed for the treatment of cardiovascular disease and diabetes in humans, could also be used to help treat very aggressive human cancers such as melanoma, pancreatic or colon cancer.”
Study co-author Professor Grant Ramm, Head of QIMR Berghofer’s Cell and Molecular Biology Department, said the findings highlight the benefits of researching a wide range of different diseases across species, because of the ultimate potential benefits for human health.
“This type of cell and molecular biology research, which is being conducted in laboratories across Australia, is critical for understanding the mechanisms of diseases and identifying new therapeutic interventions to treat not only existing health conditions, but also emerging health threats in the future,” Prof Ramm said.
“Basic science research is vital in order to generate translational outcomes in the clinic, whether it’s to treat people with chronic 21st century diseases or the Tasmanian devil with DFTD.”
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