Scientists make "food therapy" recipes for cancer patients

U.S. scientists have discovered a metabolic weakness in a variety of cancer cells that share a common characteristic: a genetic mutation in a cell machine called a shear.
In test tubes and mice, researchers found that abnormal shear function caused by the mutation weakened the chemical process of synthesized amino acid serine in cells, which required cancer cells to obtain the amino acid through an external "diet" source. When mice were fed food lacking serine, their tumors shrunk, suggesting that similar dietary interventions could help patients with the gene mutation, the researchers said. Foods rich in serine include soy, nuts, eggs, lentils, meat and shellfish.
previous studies have shown that a lack of serine in laboratory-grown cells and mice with tumors may limit the growth of cancer cells, but it is not clear which cancers the treatment may be effective against. The study's leader, W. Johns Hopkins University School of Medicine, is an assistant professor of oncology. Brian Dalton shows that data suggest that cancer cells carrying the SF3B1 mutation are best suited to try the treatment. "Now that we know that the SF3B1 mutation is the culprit, we know which patients may benefit from precision tumor therapy with low serine."
study was published in the journal Clinical Research.
SF3B1 mutations occur relatively frequently in blood cancer, including at least 30% of patients with myeloid growth syndrome (MDS), 15% of patients with chronic lymphoblastic leukemia, and 5% of patients with acute myeloid leukemia. It has a lower incidence of solid tumors such as breast, lung and prostate cancer, but the high incidence of these cancers still causes the mutation in about 100,000 patients in the United States.
SF3B1 is responsible for producing a protein as a component of the shear body, a cell machine that is critical to the proper translation of genetic code.
and colleagues first introduced the most common SF3B1 mutation gene into laboratory-grown non-cancerous human breast cells (MCF-10A).
when the protein changes were fully evaluated, the researchers found that most of the proteins that increased in content due to genetic mutations were involved in the processing of messenger RNA (mRNA), while lower-content proteins were usually involved in energy metabolism.
is actually the process by which nutrients are made from the molecular materials needed for cells to function and replicate," says Dalton, a professor at the U.S. Department of Technology. Therefore, metabolism is very important for cancer cells that are to replicate frequently. One
metabolic gene whose activity is severely affected is glyphosate dehydrogenase (PHGDH), an enzyme essential for the synthesis of amino acid serine. Because mammalian cells contain enzymes that can produce serine from other molecules, they are often considered a non-essential amino acid, meaning humans do not need to get it often through diet. Dalton wanted to know if PHGDH suppression had changed that.
to test the ability of these cells to survive without serine, the researchers bred mutant cells without serine and glycine (a prelude to serine). Under these conditions, cells grow more slowly and hardly synthesize serine and glycine.
when the researchers imported the SF3B1 mutant into human breast cancer cells (T47D), they found that PHGDH mRNA was mispped and its protein content decreased. In addition, tumor-like spheres normally formed by cells are 30 to 40 percent smaller when grown in nutritional "media" that lack serine and glycine. In introducing the SF3B1 mutation into multiple types of leukemia cells, the researchers found that cell growth was partially inhibited without serine and glycine, and that inhibition was mitigated when the loss of PHGDH was compensated by genetic or chemical methods.
, the researchers validated their findings in mice implanted with two types of human leukemia tumors. As expected, tumors grew more slowly in mice on a trisine-free/glycine-free diet.
Dalton says most cancer treatments use a drug that inhibits a specific protein, which is critical to the survival of cancer cells, but because healthy cells often need the same protein, these drugs can have many side effects. "The dependence of these SF3B1 cancer cells on external serine is a useful feature because healthy cells have the ability to produce serine, and a serine-free diet does not have much effect on them."
Dalton and colleagues are working on a feasibility study to determine whether serine levels can be safely reduced in MDS patients with SF3B1 mutations. They also plan to explore whether the number of cells carrying the mutation has decreased.
early on, the disease progressed slowly, so it's a good time to test this dietary intervention . . . If successful, we will eventually consider combining therapeutics with other standard therapies. (Source: Zhao Xixi, China Science Journal)
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