Each year, around 16,000 new instances of melanoma are detected in the United Kingdom. The NHS reports that each year approximately 16,000 new instances of melanoma are detected in the United Kingdom, making it the sixth most frequent cancer there. People under the age of 50 account for more than a quarter of all incidences of skin cancer.
With the crisis in view, Cancer researchers have made a melanoma breakthrough. Potentially a game-changer in the war against cancer, they have found a new approach to halt melanoma progression. Now they’re working to create a medication with the same effect. As documented in Nature Cell Biology, the new metabolic enzyme “shows promise” of killing cancerous cells and stalling tumor growth.
Professor Ze’ev Ronai detailed how melanoma can’t survive or grow without an enzyme called GCDH (Glutaryl-CoA Dehydrogenase), which is key to metabolizing amino acids. Scientists found that through inhibiting that enzyme, another protein called NRF2 gained the ability to suppress the cancerous cells.
Ronai clarifies that inhibiting the GCDH enzyme can lead to changes in a protein called NRF2 that can suppress cancer. Now, the quest is to find the drug, or drugs, that limit GCDH activity, potentially new therapeutics for melanoma.
Researchers have been looking into starving cancer cells to drive them to die off, as tumors grow rapidly and consume a lot of nutrients. The work is challenging, though. When cancer cells don’t find one food source, they adapt to find another.
Glutaryl-CoA Dehydrogenase (GCDH) is responsible for the metabolism of lysine and tryptophan, two amino acids crucial to human health that are also a source of sustenance for melanoma cells to manufacture energy. Melanoma cells consume lysine and tryptophan to fuel their metabolic processes, according to Dr. Sachin Verma and others.
Further experiments showed that NRF2 acquired cancer-suppressing capacity when GCDH was inhibited in rats. For Professor Ronai, NRF2 can act as both a cause of cancer and a suppressor. Not knowing how to switch NRF2’s driver role to a suppressor role was a major roadblock. Now the solution is at hand but seen as beneficial only in melanoma, not lung and breast cancers.
Since GCDH is a protein-processing enzyme, future dietary changes may be used to cure melanoma. The group is collaborating with other researchers to find GCDH inhibitors, which could be used in the future as a foundation for treating melanoma.
Dr. Verma states that using genetic techniques to inhibit GCDH is the proof of concept to hunt for small-molecule inhibitors. To that end, he and his team are looking for medicines that can block GCDH as a step toward fortifying new treatments for this melanoma breakthrough.
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