Metabolomic analysis suggests that cancer uses the same type of metabolism as roundworms. Results of joint research project (Project of Early Clinical Development for Anti-Cancer Medicine and Devices) conducted by the Super Special Consortia between the Institute for Advanced Biosciences at Keio University and the National Cancer Center Hospital East.
A group of researchers including Akiyoshi Hirayama and Professor Tomiyoshi Soga of the Institute for Advanced Biosciences (IAB), Keio University (located in the City of Tsuruoka, Yamagata Prefecture, Director General: Masaru Tomita) and Hiroyasu Esumi, Director of the National Cancer Center Hospital East (located in the City of Kashiwa, Chiba Prefecture) have used metabolomic (*1) analysis to show that the metabolism (*2) used by cancer cells to create the energy necessary for proliferation could be the same or similar to the specific type of metabolism used by parasites such as roundworms in low-oxygen environments. These are the first such findings ever made worldwide, and are the results of a joint research project entitled “Project of Early Clinical Development for Anti-Cancer Medicine and Devices” conducted between IAB Keio University and the National Cancer Center Hospital East, which was selected by the national government as a Super Special Consortia for FY2008 for supporting the development of cutting-edge medical care.
These findings were published in the 19 May, 2009 online edition of Cancer Research (American Association for Cancer Research). http://cancerres.aacrjournals.org/cgi/content/abstract/0008-5472.CAN-08-4806v1
1. Background information
In oxygen-rich environments, the vast majority of living organisms use the citric acid cycle (*3), a central part of metabolism, to produce ATP (*4), a source of energy. Parasitic roundworms inhale oxygen and use the same citric acid cycle as humans to produce energy in environments where oxygen is freely available, such as when they are growing as larvae or outside hosts. However, once they enter the small intestine where oxygen is not freely available, they use a special type of metabolism to produce energy. A certain type of anti-parasitic drugs selectively inhibits this special type of metabolism used by the parasite, which kills the parasite without causing any adverse reaction in the human host. A group of researchers led by Hiroyasu Esumi, the Director of the National Cancer Center Hospital East, discovered in 2004 that anti-parasitic drugs can kill malignant cancer cells. Based on these results and the fact that cancer cells can actively proliferate in environments with limited oxygen and no blood vessels, it was hypothesized in 2004 that cancer cells produce energy using a type of metabolism that is similar to that employed by roundworms.
2. Research findings
The research team took cancer tissue and normal tissue from colon cancer and stomach cancer patients. A comprehensive metabolome profiling of each tissue was performed by capillary electrophoresis mass time-of-flight mass spectrometry at IAB Keio University, and the metabolites of the cancer and normal tissues were compared. It was found that a high concentration of succinic acid had accumulated in cancer tissue, a phenomenon that is also observed with roundworms in oxygen-deficient environments. This accumulation of succinic acid in roundworms was only observed with the special type of metabolism (i.e. the type carried out in oxygen-deficient environments), which is strong evidence that cancer cells use the same type of metabolism. It was also revealed that a greater quantity of succinic acid had accumulated in cancers of the colon and rectum, where oxygen concentration is low, than in cancers of the stomach, where oxygen concentration is higher.
Since anti-parasitic drugs can kill cancer cells, and cancer tissue and roundworms use similar metabolic patterns for producing energy, the research project showed that the type of metabolism used by cancer cells to create the energy necessary for proliferation could be the same or similar to the special type of metabolism used by parasites such as roundworms in low-oxygen environments.
Some of the research findings were published in the 19 May, 2009 online edition of Cancer Research (American Association for Cancer Research).
The team will forge ahead with the project, aiming to identify the specific type of metabolism used by cancer cells and thereby develop a drug that selectively inhibits the key enzyme (*5) in the metabolic system. The final goal is to develop an effective anti-cancer drug with a low incidence of adverse events, since it does not act on normal tissue.
3. Researcher’s commentsHiroyasu Esumi, Director of National Cancer Center Hospital East said, “The metabolomic technologies developed by IAB Keio University are among the best in the world. Thanks to these
technologies, we have made an unexpected discovery about the properties of cancer and found a clue for developing a revolutionary anti-cancer drug.”
Professor Tomiyoshi Soga at IAB said, “We have used the metabolomic analysis technologies developed thanks to the support of Yamagata Prefecture and the City of Tsuruoka to discover a type of metabolism selectively used by cancer cells. I am delighted that this is the first step in the quest to develop a new type of anti-cancer drug.”
Explanation of technical terms*1. Metabolome
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