Metabolic Enzyme Inhibition Kills Melanoma Cells, Stops Tumor Growth
Source: Geneng News, September 2022
Researchers at Sanford Burnham Prebys have shown for the first time that inhibiting a key metabolic enzyme selectively kills melanoma cells and stops tumor growth. The team, led by Ze’ev Ronai, PhD, professor and director of the NCI-designated Cancer Center at Sanford Burnham Prebys, found that melanoma is addicted to the enzyme glutaryl-CoA dehydrogenase (GCDH), and its inhibition leads to changes in a protein called NRF2, which then acquires the ability to suppress melanoma. The studies demonstrated that genetic inhibition of GCDH expression effectively suppressed melanoma growth in culture and in mice. The team hopes that their findings could lead to a new class of drugs to selectively treat melanoma, the most severe form of skin cancer.
“We found that melanoma is addicted to an enzyme called GCDH,” said Ronai. “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.”
Ronai and colleagues published their results in Nature Cell Biology, in a paper titled, “NRF2 mediates melanoma addiction to GCDH by modulating apoptotic signaling,” in which they concluded, “Our in vivo data indicate that genetic GCDH inhibition attenuates melanoma growth, suggesting that GCDH is required for tumor cell growth, and may thus serve as a therapeutic target in this tumor.”