A new target for the development of anti-cancer drugs
Cancer has learned to starve
The discovery was made possible by identifying a mechanism that allows cancer cells to change their preferences in nutritional resources. The results of the team's work are presented in the journal Molecular Cell (Vincent et al., Mitochondrial Phosphoenolpyruvate Carboxykinase Regulates Metabolic Adaptation and Enables Glucose-Independent Tumor Growth). Briefly about the study is reported in a press release from ITMO University, received by the editorial office of <url>.
The diet of healthy cells of the body and cells affected by cancer varies greatly. The extremely rapid growth of cancer cells causes an increasing need for energy resources. This need in cells is satisfied by the absorption of glucose (sugar) – tens or even hundreds of times more than healthy cells consume. However, when glucose becomes insufficient, cancer cells are forced to look for alternative sources of nutrition to ensure their growth and survival.
Canadian, American, Russian and British scientists have studied how cells of some types of cancer, such as lung cancer, react to a lack of glucose in the environment. For the experiments, the scientists chose the most common type of lung cancer – non-small cell (85-90 percent of all cases of the disease). It turns out that when glucose becomes a scarce product, some cancer cells are able to change their food preferences and switch from glucose to the amino acid glutamine.
Figure from the article in Molecular Cell – VM
The use of glutamine as a nutritional resource is due to the fact that cancer cells begin to work with the enzyme PEPCK (mentioned in the title of the article unpronounceable for non–specialists phosphoenolpyruvate carboxykinase - VM): it is embedded in the metabolism of cells, thereby opening access to obtaining energy resources from glutamine. Thus, cells are able to continue to maintain their growth even in the absence of the main nutrient. Based on this observation, scientists were able to show that blocking the PEPCK enzyme in cancer cells can slow down tumor growth in mice. The group also managed to prove that the affected tissues of patients contain an increased concentration of PEPCK.
"Understanding the mechanisms used by cancer cells to maintain rapid growth leads to new treatment options for this disease. Targeting the ability of cells to adapt to the environment through PEPCK-linked metabolic pathways may prove to be an effective way to treat certain types of cancer," explained Alexey Sergushichev, bioinformatician and PhD student at the Department of Computer Technology at ITMO University (St. Petersburg).
The study finally confirms the presence in the body of an environment in which cancer cells compete for glucose and retain the ability to grow only when switching to other food sources.
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19.10.2015