A new study by researchers from Imperial College London suggests
statins could help fight hard-to-treat cancers.
The research reveals that tumours rely heavily on cholesterol
for growth. Cholesterol-lowering statins - which are currently
prescribed to around 30 million people worldwide, can block this
supply - causing it to 'starve' and die.
The team behind the research focused on oestrogen-receptor
positive breast cancers. These make up over 70 per cent of all
breast cancers, and are fuelled by the hormone oestrogen, which
binds to the oestrogen receptor inside cancer cells where triggers
growth.
These cancers are usually treated with surgery to remove the
tumour, followed by a course of targeted chemotherapy.
However, many cancers eventually become resistant to these
treatments - and so patients see their cancer return - although it
is unknown why.
Earlier work has suggested women with breast cancer who take
statins have fewer relapses, and so the team decided to examine
cholesterol production in breast cancer cells.
By performing tests on cancer cells in the lab, and studying the
activity of genes involve in cholesterol production, the team
discovered cancer cells can increase their production of
cholesterol, especially once they become resistant to chemotherapy.
All cells in the body produce small amounts of cholesterol - as it
is crucial to survival - but the study suggests drug resistant
cancer cells turbo charge their cholesterol-making machinery.
This cholesterol provides cancer cells with an alternate source
of fuel, meaning they are no longer reliant on oestrogen to grow -
and the cancer becomes resistant to the chemotherapy.
Using mouse models and three dimensional cell systems, the team
showed statins may be able to target cholesterol production in
drug-resistant cancer cells, and slow growth.
However, the scientists caution that simply taking a statin
alongside normal cancer treatment would have no effect as not
enough of the statin would reach the cancer cells.
But because the team identified genes associated with
turbo-charged cholesterol production, they suggest doctors could
one day test breast cancer patients for these genes. If the genes
were found to be switched on, it could influence a doctor's choice
of chemotherapy, explains Dr Luca Magnani of Imperial's Department
of Surgery and Cancer.
"If a doctor sees from a patient's genetic tests that their
cancer cells have highly active cholesterol-making machinery, then
they may chose Tamoxifen, since it binds to the estrogen receptor
and stops the cell growing even in the presence of high cholesterol
levels. There is no point in choosing the alternative treatment -
aromatase inhibitors - which lowers the amount of oestrogen in the
blood, as the cancer has already found an alternate source of fuel.
It's like trying to stop a car by blocking the supply of gasoline,
but the engine has already switched itself over to diesel. However,
if you use Tamoxifen, you're jamming the engine altogether."
He adds that human studies are now needed to confirm these
findings.
The paper, Differential epigenetic reprogramming in response to specific
endocrine therapies promotes cholesterol biosynthesis and cellular
invasion, is published in Nature Communications.