Cancer’s ‘Achilles’ Heel’ has been identified by scientists.
The protein fuels tumours when oxygen levels are low, say scientists.
It enables them to adapt and survive – and become more aggressive.
The enzyme called CAIX (Carbonic Anhydrase IX) helps diseased cells spread to other organs.
It could hold the key to new treatments for the deadliest forms including breast, pancreatic, lungs, bowel and prostate cancers.
Study senior author Professor Shoukat Dedhar, of the University of British Columbia in Canada, said: “Cancer cells depend on the CAIX enzyme to survive, which ultimately makes it their ‘Achilles’ heel.’
“By inhibiting its activity, we can effectively stop the cells from growing.”
The findings, published in the journal Science Advances, will help researchers develop drugs that destroy solid tumours. These are the most common types that arise in the body. They rely on blood supply to deliver oxygen and nutrients to help them grow.
As the tumours advance, the blood vessels are unable to provide enough to every part.
Over time, the low-oxygen environment leads to a buildup of acid inside the cells.
They overcome the stress by unleashing proteins, or enzymes, that neutralise the acidic conditions.
The process is behind spread, or metastasis, to other organs – which is what kills patients.
Finding a way to prevent it is the ‘Holy Grail’ of cancer research – turning it into a chronic, rather than fatal, illness. One of the enzymes is CAIX.
The Canadian team previously identified a unique compound known as SLC-0111 as a powerful inhibitor.
It is currently being tested in clinical trials. Experiments in mice with breast, pancreatic and brain cancers showed its effectiveness.
It suppressed tumour growth and spread although there were side effects, with other cellular properties diminished.
Now the researchers have demonstrated other weaknesses in CAIX using a technique called genome-wide synthetic lethal screening.
The powerful tool systematically deletes one gene at a time to determine if a cancer cell can be killed by eliminating the enzyme.
Surprisingly, results pointed to an unexpected role of proteins and processes that control a form of cell death called ferroptosis.
It happens when iron builds up and weakens a tumour’s metabolism and cell membranes.
Dr Dedhar added: “We now know the CAIX enzyme blocks cancer cells from dying as a result of ferroptosis.
“Combining inhibitors of CAIX, including SLC-0111, with compounds known to bring about ferroptosis results in catastrophic cell death and debilitates tumour growth.”
A large international effort is currently underway to identify drugs that induce ferroptosis. The study is a major step forward in this quest.
For more stories from where you live, visit InYourArea.