A current study conducted by researchers at NYU Langone Medical Center, the Laura and Isaac Perimutter Cancer Center, and the Massachusetts General Hospital has shown promising results for the treatment of a particular type of brain tumor using experimental cell metabolism drugs. The researchers chose to focus on a brain tumor known as low-grade glioma due to the fact that over 70% of these cancer cells were found to contain a targetable mutation. This mutation is located in the genetic makeup of an enzyme known as isocitrate dehydrogenase, or IDH1. The IDH1 mutations are known to cause a metabolite called 2-hydroxyglutarate to accumulate, which promotes cell growth by interfering with DNA methylation patterns and eventually prevents tumor suppression.
Image Source: dra_schwartz
The cells in brain tumors with the IDH1 mutation were found to have significantly lower levels of NAD, a metabolic chemical that turns nutrients into energy for repairing DNA. Researchers hypothesized that if the NAD levels in these cells were further decreased to a certain threshold, the cells would eventually run out of energy and die. In order to test this hypothesis, researchers evaluated the effect of experimental drugs on the growth rate of IDH1-mutated tumors. The researchers first implanted human IDH1-mutated cancer cells that contained lower levels of NAD into mice. Next, the research team administered drugs, known as NAMPT inhibitors, which were known to reduce NAD levels. They found that the experimental drugs halted the growth of the tumors in the mice, further extending the lifespan of the mice with the mutant IDH1 brain tumors.
The research team concluded that cancer cells with IDH1 mutations were killed by the NAMPT inhibitors, due to the further reduction of already low levels of NAD, causing the cells to run out of energy. Thus, the experimental drugs that changed this energy supply in cells were concluded to, in fact, slow overall brain tumor growth. The researchers plan to launch clinical trials in cancer patients with IDH1-mutated cancers within three years. There are currently no curative treatments for IDH1 gliomas, and nearly all patients die from such a brain cancer. Thus, the discovery of the impact of NAMPT inhibitors against IDH1-mutated cancers could lead to an incredible advancement in the field of cancer research.
Feature Image Source: DNMT1 by Enzymlogic
