Computer model reveals cancer's energy source

August 1, 2014 by Krishna Ramanujan, Cornell University
Whole-body PET scan using radioactive glucose to show liver metastases of a colorectal tumor. Doctors inject patients with radioactive glucose and then watch where it is consumed; tumors are a major source of consumption. Credit: Jens Maus

(Medical Xpress)—A computer model study reveals – for the first time – details of an energy-creating process vital and unique to cancer cells. The research holds promise for new interventions and for personalizing cancer treatments based on individual needs.

The findings, which will revise basic biochemistry textbooks, focused on the energy-making process in cancer cells known as the Warburg Effect.

The Cornell-led study, published July 9 in the journal eLife, revealed that some of the enzymes thought to have no effect on the Warburg Effect, in fact, play a large role: An enzyme called GAPDH influences many parts of a cancer cell's energy-making pathway.

"Our findings open opportunities for new ways to intervene in the Warburg Effect," said Jason Locasale, the paper's senior author and assistant professor of nutritional sciences in Cornell's College of Agricultural and Life Sciences. Alexander Shestov, a former senior research associate, and Xiaojing Liu, a postdoctoral fellow, both in Locasale's lab, are the paper's lead authors. The results also "provide glimpses into whether we have predictive capacity to discern if treatments might be working," Locasale added.

All multicellular organisms evolved pathways that take nutrients, sugars and oxygen and make energy through respiration and chemical processes. In , this energy-making process is known as . But when cells evolve cancerous properties and grow uncontrollably, they instead ferment their sugars to create energy even in the presence of oxygen. This process is called aerobic glycolysis, or the Warburg Effect.

The new findings are an important step toward developing a drug that affects only fermentation and not the normal metabolism of glucose, thereby depriving of energy. The new model lays groundwork for predicting whether treatments will be effective based on an individual's unique metabolism.

Still, very few details have been known about the Warburg Effect. "We can now systematically perturb anything in the [computer] model and identify important components" of the Warburg Effect, Locasale said.

Dating back to work by Efraim Racker, a Cornell researcher who made seminal discoveries in the area in the 1970s, followed by advances in cancer and genetic research, it is "known now that almost every cancer gene has some capacity to induce the Warburg Effect," making it fundamental to proliferative diseases, Locasale said.

Currently, the Warburg Effect is used in clinical practice to diagnose and monitor cancer. Doctors inject patients with radioactive glucose and then watch where it is consumed; tumors are a major source of consumption. Researchers are also exploring whether dietary interventions with less sugar and the use of diabetes drugs that lower glucose may impact the Warburg Effect to treat cancer.

Explore further: Discovery of a mechanism that makes tumor cells sugar addicted

Related Stories

Discovery of a mechanism that makes tumor cells sugar addicted

April 4, 2014
For almost a hundred years ago is known that cancer cells feel a special appetite for a type of sugar called glucose. The tumor uses this molecule is like the gasoline which depends a sports car to burn faster and grows and ...

Lactate metabolism target halts growth in lung cancer model

April 10, 2014
Cancer cells generate energy differently than normal cells, a characteristic that helps them to survive and metastasize. A major goal in the field of cancer metabolism is to find ways to overcome this survival advantage.

Targeting cancer's sweet tooth

October 21, 2013
Ludwig researchers have elucidated a key mechanism by which cancer cells change how they metabolize glucose to generate the energy and raw materials required to sustain runaway growth.

Study reveals new molecular target for melanoma treatment

August 17, 2012
A laboratory study led by UNC medical oncologist Stergios Moschos, MD, demonstrates how a new targeted drug, Elesclomol, blocks oxidative phosphorylation, which appears to play essential role in melanoma that has not been ...

Link between colon cancer and metabolism identified

May 13, 2014
More than 60 years ago Otto Warburg recognized that cancer cells differ from normal cells in the metabolic pathway they use for the oxidation of sugar. Rather than the typical series of oxidative steps that take place in ...

Mdm2 suppresses tumors by pulling the plug on glycolysis

February 24, 2014
Cancer cells have long been known to have higher rates of the energy-generating metabolic pathway known as glycolysis. This enhanced glycolysis, a phenomenon known as the Warburg effect, is thought to allow cancer cells to ...

Recommended for you

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

More evidence of link between severe gum disease and cancer risk

January 16, 2018
Data collected during a long-term health study provides additional evidence for a link between increased risk of cancer in individuals with advanced gum disease, according to a new collaborative study led by epidemiologists ...

Researchers develop a remote-controlled cancer immunotherapy system

January 15, 2018
A team of researchers has developed an ultrasound-based system that can non-invasively and remotely control genetic processes in live immune T cells so that they recognize and kill cancer cells.

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.