Combining new drugs with dietary changes could help to break down cancer’s reliance on fat for growth, according to UK research published last night.
Researchers, led by scientists at The Institute of Cancer Research, London, and colleagues at Imperial College London, found that targeting cancer’s ability to process fat using a new class of drugs could halt tumour growth in mice, but only when combined with a diet free of fats.
They say their findings open up the possibility of ‘drugs and diet’ cancer treatments that combine precision medicine with a specific new class of drugs and dietary changes.
They also point to the potential for the iKnife to pick out tumours with the metabolic weakness during surgery, by analysing the smoke given off as tissue is burned during excisions.
Scientists looked at cancer cells in the lab and patient-derived tumours to search for metabolic fingerprints, using an analytical function connected to the iKnife to sift through the smoke from vaporised tissue for crucial clues about cellular metabolism.
Writing in Cell, the team says the molecule PI3K, which is vital to the growth and survival of cancer cells, was found to have a key role in triggering the release of arachidonic acid.
They found that the mutant form of PI3K, which is often found in cancers, cause a chain of events involving cPLA2, which releases arachidonic acid. This helps to fuel the uncontrolled growth and spread of cancer.
Using a mouse model, they established that cPLA2 inhibitors, a new class of drugs in clinical trials for the treatment of a number of inflammatory conditions, could be adapted to treat fat-reliant cancers.
However, the drugs worked only when it was combined with a fat-restricted diet: when the mice were treated with a drug that inhibits cPLA2 and were given a plant-based, fat-free diet, tumours with mutant PI3K stopped growing and spreading.
However, when mice were fed a ‘Western’ diet high in omega-6 fatty acids, the cPLA2 inhibitor was not effective, leading to them to suggest that arachidonic acid could be a metabolic biomarker.
Dr George Poulogiannis, leader of the Signalling and Cancer Metabolism Team at The Institute of Cancer Research, London, said: “We have known for a long time that cancers have genetic weaknesses that can be targeted by treatment – but our study shows that they can also be prone to specific metabolic vulnerabilities.
“Our study shows that stopping a specific subtype of cancers from being able to release a key omega-6 fat known as arachidonic acid could be effective as a treatment, but only if sources of this fat are also cut out of the diet. These findings in mice therefore highlight the role of nutrition in the response to the proposed drug therapy.
“We also show that analysing cancer’s metabolic fingerprint can be a key tool in understanding, diagnosing and treating the disease.
"Our research raises the prospect that in future we could analyse cancer’s metabolic fingerprint while patients are on the operating table using the iKnife, and where appropriate match them to a combined drug and diet treatment.”
Describing the findings as “exciting”, Professor Paul Workman, chief executive of The Institute of Cancer Research, London, said the study opens up a new approach for treating cancer that targets differences between the metabolism of tumours and that of healthy tissue.
Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids. Cell 18 June 2020
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