Huge progress - scientists stopped the growth of melanoma cells

Melanoma is one of the most common cancers. Skin melanoma is the 17th most common cancer in the world. This is the 13th most common cancer in men and the 15th most common cancer in women. [ref. 1] 

It is the most severe form of skin cancer, but US scientists have proved for the first time that a metabolic enzyme is a promising means of destroying cancer cells and stopping tumor growth. This is a huge step forward in the fight against cancer, even if it is too early for more definitive conclusions. 

Researchers from Sanford Burnham Prebys, led by Ze'ev Ronai, Ph.D., have shown for the first time that inhibiting a key metabolic enzyme selectively kills melanoma cells and stops tumor growth. Published in Nature Cell Biology, these findings could lead to a new class of drugs to selectively treat melanoma, the most severe form of skin cancer. Scientists hope this could be a step towards developing drugs to treat aggressive cancer.  [Ref. 2] 

"We found that melanoma is addicted to an enzyme called GCDH. If we inhibit the enzyme, it leads to changes in a key protein called NRF2, which acquires the ability to suppress cancer. Now our goal is to find a drug or drugs that limit the activity of GCDH, potentially new melanoma therapists .

As tumors grow rapidly and require a lot of resources to feed, researchers are exploring ways to force cancer cells to "starve." The bad news is that, however promising this approach may be, deprived of one source of food, cancers invariably find another.

GCDH, which means glutaril-coA dehydrogenase, plays an important role in the metabolism of lysine and Tryptophan - amino acids that are essential for human health. When the Ronai laboratory began to study how melanoma cells generate energy from lysine, they discovered that GCDH was critical to this process.

"Melanoma cells "eat" lysine and Tryptophan to produce energy," says Sachin Verma, Ph.D., a postdoctoral author at the Ronai Laboratory and first author of the study. 

"However, harnessing the energy from this path requires cancer cells to suppress 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 that only one of these enzymes is crucial, GCDH. Melanoma cells cannot survive without the presence of GCDH."

Further study shows that inhibition of GCDH in an animal model gives NRF2 properties to suppress cancer.

"We have known for a long time that NRF2 can be both an engine and a suppressor of cancer," the author says. "We just didn't know how we were converting NRF2 from driver to suppression function. Our current study identifies the answer."

The researchers also found that inhibition of GCDH is quite selective for melanoma tumors. Similar efforts in lung, breast and other cancers have not had an effect, possibly because these cancers may be addicted to other enzymes.

From a therapeutic point of view, the study reveals several possible options. Although animal models without GCDH were mainly normal, they could not tolerate a high-protein diet. This is important because the tumors of some melanoma patients also have a low GCDH. 

Given the role of the enzyme in protein processing, the authors believe that GCDH poor tumors may also be vulnerable to foods high in protein, creating a potential dietary treatment. In addition, a decrease in GCDH levels in tumors can be supplemented with selected protein diets.