Possible treatment against melanoma by Inhibiting key metabolic enzyme

For the first time, Sanford Burnham Prebys researchers have demonstrated that inhibiting a crucial metabolic enzyme specifically kills melanoma cells and inhibits tumour growth. These findings which were published in Nature Cell Biology, may help develop a new class of medications that target melanoma, the most dangerous type of skin cancer.

"We found that melanoma is addicted to an enzyme called GCDH," says Ronai, professor and director of the NCI-designated Cancer Center at Sanford Burnham Prebys. He added that "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 tumors grow rapidly and require lots of nutrition, researchers have been investigating ways to starve cancer cells. As promising as this approach may be, the results have been less than stellar. Denied one food source, cancers invariably find others.

GCDH, which stands for Glutaryl-CoA Dehydrogenase, plays a significant role in metabolizing lysine and tryptophan, amino acids that are essential for human health. When the Ronai lab began interrogating how melanoma cells generate energy from lysine, they found GCDH was mission-critical.

Further exploration showed that inhibiting GCDH in an animal model gave NRF2 cancer- suppressing properties.

Ref:

ZE'EV RONAI, et al,Nature Cell Biology, DOI: 10.1038/s41556-022-00985-x