Researchers from Sanford Burnham Prebys located in California have proved previously for the first time blocking an important metabolic en...
Researchers from Sanford Burnham Prebys located in California have proved previously for the first time blocking an important metabolic enzyme kills cancerous cells and slows the growth of tumors. The study, which was presented in Nature Cell Biology, reveals that these results could lead to the development of an entirely new class of drugs to treat melanoma selectively.
The most common form of skin cancer is the frequent type of cancer. While melanoma is only 1 percent of skin cancers, it is responsible for the majority of deaths from skin cancer.
Taking away GCDH starves tumors
As tumors multiply rapidly and require plenty of "fuel" in order to expand, researchers are looking for methods to kill cancer cells. Although, as effective as the method may seem however, the results have not been more than ideal. If doctors reject one the food sources, they tends to will find another.
Professor. Ronai explains that Glutaryl-CoA Dehydrogenase (GCDH) is an "significant" role in metabolizing tryptophan and lysine. These are amino acids that are vital for the health of humans. When the team began to research the way that melanoma cells create energy from lysine they realized it was GCDH could be "mission-critical."
"Melanoma cells 'eat' lysine and tryptophan to produce energy," claims the lead writer Sachin Verma Ph.D. is a postdoctoral scientist at the Ronai lab. "However the process of harnessing energy from this process requires cancer cells to eliminate the toxic waste generated during this process. It's a 6-step process and we assumed that the cells would require each of the six enzymes. It turns out that only one enzyme is essential, GCDH. Melanoma cells are not able to be sustained without GCDH component that is part of this pathway."
Animal studies showed that inhibiting GCDH created NRF2 cancer-suppressing characteristics.
"We've known for a long time that NRF2 can be both a driver and a suppressor of cancer," Ronai declares. "We were unsure of what we could do to convert NRF2 into a function that is driver into a suppressor functions. The current study provides the solution."
The treatment is ineffective with other cancers.
The authors of the study also observed that inhibiting GCDH specifically targeted the melanoma tumors. Similar studies on breast, lung, and other types of cancer did not have the same effect. The team is of the opinion that those cancers could be dependent on different enzymes. The team suggests that GCDH-deficient tumors might also be susceptible to foods high in protein which could lead to a food-based therapy for the treatment of skin cancer.
Ronai lab Ronai lab is currently working with scientists from the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys to identify small-molecule GCDH inhibitors that could serve as the basis for future treatments for melanoma.
"In the study, we used genetic approaches to inhibit GCDH, which provide the proof of concept to search for small molecules inhibitors," Verma concludes. "Indeed, we are actively searching for potential drugs that could inhibit GCDH, which would be candidates for novel melanoma therapies."
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