Feed a cold -- starve a tumor

October 21, 2011

The condition tuberous sclerosis, due to mutation in one of two tumor suppressor genes, TSC1 or TSC2, causes the growth of non-malignant tumors throughout the body and skin. These tumors can be unsightly and cause serious damage to organs. Growth of tumors in the brain may cause seizures and in the kidney, liver or heart, tumors can disrupt normal function, to the extent of causing the organ to fail. New research published in BioMed Central's open access journal Cell and Bioscience shows that the growth of glucose-dependent TSC-related tumors can be restricted by 2-deoxyglucose, which blocks glucose metabolism, but not by restricting dietary carbohydrates.

TSC1 and TSC2 normally inhibit the mTOR signaling pathway but if the TSC genes are mutated, so that they no longer function, unregulated mTORC1 drives glycolysis and cell growth. Rapamycin works by blocking mTORC1 and is currently used to treat tuberous sclerosis. However, rapamycin is an immunosuppressant and can have significant side effects, especially when used long term. A group of researchers from the University of Washington, led by Prof Yeung, looked in detail at the potential of blocking cell proliferation by directly reducing glycolysis.

Surprisingly TSC2-negative tumors in mice kept on an unrestricted carbohydrate-free diet grew bigger than those on a western-style diet. However the glucose analogue, 2-deoxyglucose (2DG), which disrupts , reduced the tumor size in mice on either diet. Prof Yeung explained, "Treatment with 2DG significantly reduced the rate at which the tumor cells divided, especially when paired with a diet which contained carbohydrates. This combination of 2DG and a western-style diet imposed the greatest energy stress on the tumors and correlated with the lowest levels of serum glucose. On the other hand, while the carbohydrate-free (and high-fat) diet provided enough to sustain tumor growth, some of the appeared toxic to the tumor cells. This in turn led to an accumulation of liquefied, necrotic materials that contributed to greater tumor size."

Compounds such as 2DG are able to inhibit TSC2-negative tumor growth by restricting glycolysis in a manner not seen by reducing dietary glucose. 2DG is currently undergoing trials for use in prostate cancer. This and other metabolic interventions hold promise for future cancer treatment.

Explore further: Low-carbohydrate, high-protein diets may reduce both tumor growth rates and cancer risk

More information: Glucose deprivation in Tuberous Sclerosis Complex-related tumors. Xiuyun Jiang, Heidi L Kenerson and Raymond S Yeung, Cell & Bioscience (in press)

Related Stories

Low-carbohydrate, high-protein diets may reduce both tumor growth rates and cancer risk

June 14, 2011
Eating a low-carbohydrate, high-protein diet may reduce the risk of cancer and slow the growth of tumors already present, according to a study published in Cancer Research, a journal of the American Association for Cancer ...

Metabolic shift may offer early cancer clue

July 5, 2011
Cancer cells are well known for their altered metabolisms, which may help them generate the energy they need for rapid growth. Using an emerging imaging technology, researchers reporting in the July Cell Metabolism, a Cell ...

Recommended for you

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

A metabolic treatment for pancreatic cancer?

August 15, 2017
Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.