Scientists found that the cancer is ‘addicted’ to an enzyme which they are now trying to inhibit
Scientists have discovered a new way to stop the growth of melanoma, in what could be a major breakthrough in the fight against cancer. And they’re now hoping to develop a drug that can do the same.
Melanoma is one of the most common cancers in the UK, seeing about approximately 16,000 new cases diagnosed every year.
According to the NHS, melanoma is the fifth most common cancer in the UK, with around 16,000 new cases diagnosed every year. More than a quarter of skin cancer cases are diagnosed in people under 50.
Scientists in the US, who published their findings in the journal, Nature Cell Biology, have now discovered that a metabolic enzyme “shows promise” that it can kill cancerous cells and stop tumour growth.
The leader of this study, Professor Ze’ev Ronai detailed how melanoma can’t survive or grow without an enzyme called GCDH (Glutaryl-CoA Dehydrogenase), which is key to metabolising amino acids. Scientists found that through inhibiting that enzyme, another protein called NRF2 gained the ability to suppress the cancerous cells.
“We found that melanoma is addicted to an enzyme called GCDH,” Ronai, professor and director of the NCI-designated Cancer Center at Sanford Burnham Prebys explained.
“If we inhibit the enzyme, it leads to changes in a key protein, called NRF2, which acquires its ability to suppress cancer. Now, our goal is to find a drug, or drugs, that limit GCDH activity, potentially new therapeutics for melanoma.”
Because tumours grow rapidly and require lots of nutrition, researchers have been investigating ways to starve cancer cells in order to send them into decline. However, it isn’t easy work. Denied one food source, cancers invariably find others.
GCDH – or Glutaryl-CoA Dehyrogenase – metabolises two key amino acids essential to keep us healthy – lysine and tryptophan – but also provide a source of nutrition for melanoma cells to produce energy.
Another researcher, Sachin Verma, explained that Melanoma cells eat lysine and tryptophan to produce energy.
“However, harnessing energy from this pathway requires cancer cells to quench toxic waste produced during this process.
“It’s a six-step process, and we thought the cells would need all six enzymes. But it turns out only one of these enzymes is crucial, GCDH. Melanoma cells cannot survive without the GCDH portion of the pathway.”
From further experimentation, the scientists discovered that when stopping GCDH in animals, NRF2 gained cancer-suppressing ability.
Professor Ronai said: “We’ve known for a long time that NRF2 can be both a driver and a suppressor of cancer.
“We just didn’t know how we could convert NRF2 from a driver to a suppressor function. Our current study identifies the answer.”
So far, the benefits have only been shown in melanoma, with lung and breast experiments showing no effect.
There could also be a dietary treatment for melanoma in future, given that GCDH is a protein-processing enzyme. The team are working with other scientists to identify the GCDH inhibitors that could form the basis for melanoma treatment in future.
Dr Verma added: “In the study, we used genetic approaches to inhibit GCDH, which provide the proof of concept to search for small-molecule inhibitors, “Indeed, we are actively searching for potential drugs that could inhibit GCDH, which would be candidates for novel melanoma therapies.”
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