Study provides first systematic survey of metabolites across tumor types

January 25, 2018, Dana-Farber Cancer Institute

In an advance reminiscent of the earliest maps of genomic mutations in cancer, investigators at Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center have completed the first systematic survey of the products of biochemical reactions within cancer and their relation to the progress of the disease. The products, known as metabolites, arise from the myriad chemical reactions that keep cells alive and functioning.

Published online today by the journal Cell Systems, the survey results provide scientists around the world with a curated dataset with which to track in cancer and potentially uncover vulnerabilities that can be targeted by novel therapies. A website accompanying the new report enables researchers to study patterns of variation in levels across multiple types of cancers, explore how these patterns change as cancers progress, and look for connections between metabolites and drug susceptibility.

"Scientists have known for more than 100 years that metabolic changes are important in cancer, but over the last three decades the field has been dominated by discoveries of the genetic and genomic changes that occur in cancer cells," says the study's senior author, Chris Sander, PhD, of Dana-Farber. "In the last five to 10 years, there has been a resurgence of cancer metabolism research - with a focus on the differences in the metabolic functioning of cancer cells vs. normal cells - and in using that knowledge as the basis for new therapies. The drug methotrexate and, more recently, drugs that inhibit enzymes such as glutaminase or isocitrate dehydrogenase, are excellent examples. We think there is more to come."

The revival has been propelled in part by technological advances that enable scientists to identify large numbers of the metabolites present in normal and cancerous cells - much as advances 20 years ago have made it possible to canvas cells for hundreds or thousands of genomic irregularities.

Metabolism is the catchall term for processes that drive every aspect of cell life - consuming energy, growing, dividing, and performing specific functions within the body. It is as basic to the life of as to cancer cells, although their metabolisms can differ in a variety of ways. Much of cell metabolism involves chemical reactions sparked by enzymes. The products of these reactions are metabolites, which themselves can interact to form other metabolites. The assortment of metabolites within a cell is referred to as its metabolome.

For the current study, researchers built a broad dataset of cancer cell metabolites by merging data from 11 studies involving more than 900 tissue samples and seven different cancer types. Their analysis of the data showed that the composition of metabolites in normal tissue is often far different from that in corresponding types of tumor tissue. Across many tumor types, however, the investigators found that several metabolites showed consistent increases or decreases in abundance compared to normal tissue.

The researchers also collected data on the stage and grade of each tumor (measures of tumor progression and aggressiveness). By linking this data to the metabolite data, they found that a small number of metabolites were associated with aggressive tumors in many cancer types. One such metabolite, kynurenine, which was elevated in aggressive tumors regardless of where they originated, is known to help cells evade an attack from the immune system. "Our findings offer the most comprehensive look to date at the differences in metabolic programming between normal and , and across various kinds of cancer," says Ed Reznik, PhD, of Memorial Sloan Kettering, the co-lead author of the study with Augustin Luna, PhD, of Dana-Farber. "We expect the metabolomics dataset will be an important tool as the field of metabolism moves forward."

Explore further: Metabolic profiles essential for personalizing cancer therapy

Related Stories

Metabolic profiles essential for personalizing cancer therapy

February 7, 2012
One way to tackle a tumor is to take aim at the metabolic reactions that fuel their growth. But a report in the February Cell Metabolism shows that one metabolism-targeted cancer therapy will not fit all. That means that ...

Elucidating the role of circulating nutrients that fuel tumor growth

October 19, 2017
Tumors acquire nutrition necessary for generating energy and building blocks for growth and survival from the body of the patient in which they reside.  Although these nutrients are predominantly provided by the circulating ...

Amino acid consumption associated with how fast cancer cells divide

May 24, 2012
For almost a century, researchers have known that cancer cells have peculiar appetites, devouring glucose in ways that normal cells do not. But glucose uptake may tell only part of cancer's metabolic story. Researchers from ...

Testing blood metabolites could help tailor cancer treatment

June 3, 2016
Testing for metabolic changes in the blood could indicate whether a cancer drug is working as designed, a new study reports.

Pancreatic cancer cells find unique fuel sources to keep from starving

August 10, 2016
Pancreatic cancer cells avert starvation in dense tumors by ordering nearby support cells to supply them with an alternative source of nutrition. This is the finding of a study in cancer cells and mice published August 10 ...

Recommended for you

New drugs are improving survival times for patients with aggressive type of blood cancer, study finds

June 25, 2018
Survival times for a highly aggressive type of blood cancer have nearly doubled over the last decade due to the introduction of new targeted drugs, a Yorkshire study has shown.

Dying cancer cells make remaining glioblastoma cells more aggressive and therapy-resistant

June 21, 2018
A surprising form of cell-to-cell communication in glioblastoma promotes global changes in recipient cells, including aggressiveness, motility, and resistance to radiation or chemotherapy.

Existing treatment could be used for common 'untreatable' form of lung cancer

June 21, 2018
A cancer treatment already approved for use in certain types of cancer has been found to block cell growth in a common form of lung cancer for which there is currently no specific treatment available.

Novel therapy makes oxidative stress deadly to cancer

June 21, 2018
Oxidative stress can help tumors thrive, but one way novel cancer treatments work is by pushing levels to the point where it instead helps them die, scientists report.

Researchers uncover new target to stop cancer growth

June 21, 2018
Researchers at the University of Wisconsin-Madison have discovered that a protein called Munc13-4 helps cancer cells secrete large numbers of exosomes—tiny, membrane-bound packages containing proteins and RNAs that stimulate ...

Higher body fat linked to lower breast cancer risk in younger women

June 21, 2018
While obesity has been shown to increase breast cancer risk in postmenopausal women, a large-scale study co-led by a University of North Carolina Lineberger Comprehensive Cancer Center researcher found the opposite is true ...

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.