In what researchers believe is an important step toward gaining a more complete picture of cancer metabolism, scientists at Columbia University Medical Center have identified multiple metabolic expression changes associated with cancer as well as hundreds of new potential drug targets that could cut off a tumor's fuel supply or interfere with its ability to produce essential building blocks.
"So far, people have focused mainly on a few genes involved in major metabolic processes. Our study provides a comprehensive, global view of diverse metabolic alterations at the level of gene expression," Dennis Vitkup, associate professor of biomedical informatics at CUMC and the study's lead investigator, said in a statement.
Researchers analyzed gene expression data from 22 tumor types and found multiple metabolic expression changes associated with cancer--notably, that tumor-induced expression changes are significantly different across diverse tumors. They observed that some metabolic changes--such as an increase in nucleotide biosynthesis and glycolysis--seem to be more frequent across tumors. But other metabolic changes, like fluctuations in oxidative phosphorylation, are varied across tumors.
The researchers also found that expression changes can mimic or cooperate with cancer mutations that contribute to tumor formation. For example, in cancers such as glioblastoma and acute myeloid leukemia, mutations in the enzyme isocitrate dehydrogenase are known to produce a specific metabolite called 2-hydroxyglutarate that promotes tumor growth. The Columbia team found that the expression of the enzyme increases substantially in tumors with the recurrent mutations. This overexpression could cause an overproduction of 2-hydroxyglutarate.
During the analysis, the team also pinpointed hundreds of differences between normal and cancer cells' use of isoenzymes--enzymes that catalyze the same chemical reactions but have different kinetic properties--that could be potential new drug targets. The study was published in the online edition of Nature Biotechnology.
"Inhibiting specific isoenzymes in tumors may be a way to selectively hit cancer cells without affecting normal cells, which could get by with other isoenzymes," Jie Hu, a postdoctoral researcher at Columbia and first author of the study, said in a statement.
In the early 20th century, cancer research was dominated by the study of cancer metabolism. The field, as of late, is going through a bit of a resurgence--with companies like Agios Pharmaceuticals and Advanced Cancer Therapeutics focusing on cancer metabolism.
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