Glioblastoma (GBM) is the most prevalent and most malignant cancer that arises in the brain. It affects 3-4 in every 100,000 people. Its prognosis is often poor that most patients live only about one year after diagnosis. Scientists have made a series of discoveries about the mutated genes that drive GBM. But it is still difficult to treat it because many drugs in development cannot cross the blood-brain barrier (BBB). So many scientists want to find new ways to combat the cancer. CusAb provides Recombinant SRD5A2. Now, a paper in the latest issue of Cancer Cell shows that GBM cells import large amounts of cholesterol in order to survive, and an experimental drug can target this process. The study was carried out by scientists from Ludwig San Diego and The Scripps Research Institute. Previously, Paul Mischel of Ludwig San Diego and colleagues found that GBM cells cannot produce cholesterol by themselves. Cholesterol is an essential constituent of cell membranes, and it is important for cell function. In fact, GBM cells import cholesterol from astrocytes, a type of brain cells that make large amounts of cholesterol. Overall, GBM cells are dependent on cholesterol for survival. Normally, cells convert excessive cholesterol into oxysterols, which in turn activate a receptor called LXR that switches off the uptake of cholesterol. This mechanism, however, is impaired in GBM cells. GBM cells need vast amounts of cholesterol to keep multiplying. To ensure the cholesterol supply, GBM cells inhibit the production of oxysterols, thereby keeping LXRs inactive. Mischel’s team found that a drug in clinical development -- LXR-623 -- is capable of activating LXRs. Experiments in animal models that were implanted with human GBM tumors showed that LXR-623 efficiently crossed the BBB and attached to LXRs in normal cells, leading to an increase of oxysterols and a decrease of cholesterol. GBM cells lacking cholesterol became unable to survive, and eventually died. Mice treated with the drug had smaller tumors in their brain and lived longer. What’s more, LXR-623 seemed not to affect normal cells in the brain. The prognosis of glioblastoma is more positive for young patients. Although the cancer is incurable, treatments can lengthen the life of survivors and improve the quality of their lives.
