Summary of New Investigational Drug Could Combat Brain Tumors:
Researchers at Massachusetts General Hospital have found that an investigational drug named YTX-7739, which disrupts the conversion of carbohydrates to fats, can slow down tumor growth and increase the sensitivity of glioblastoma cells to anticancer treatments in mice. The drug works by blocking the enzyme stearoyl CoA Desaturase 1 (SCD), which is involved in the process of de novo lipid synthesis. Additionally, the team found that the MEK/ERK signaling pathway renders glioblastoma cells particularly vulnerable to YTX-7739, while the AMPK signaling pathway can make them resistant. The findings may lead to new treatment options for patients with glioblastoma, a highly aggressive and lethal type of brain cancer.
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Innovative Drug YTX-7739 Shows Promise in Treating Glioblastoma
Glioblastoma, a type of brain cancer, is one of the most aggressive and lethal forms of cancer. Despite advances in treatment, it is often resistant to traditional therapies. In an effort to find new treatment options, researchers from Massachusetts General Hospital (MGH) explored the possibility of targeting de novo lipid synthesis, a process by which glioblastoma cells meet their energy needs.
The team tested the anti-glioblastoma potential of an SCD inhibitor, YTX-7739, that can cross the blood-brain barrier and is being evaluated as an oral drug in phase I clinical trials for the treatment of patients with Parkinson’s disease. The results, published in Science Translational Medicine, showed that YTX-7739 was toxic to patient-derived glioblastoma stem cells. When administered to mice with tumors, YTX-7739 inhibited processes involved in fatty acid metabolism in glioblastoma cells and increased the cells’ sensitivity to conventional glioblastoma chemotherapy.
How YTX-7739 Works
YTX-7739 works by blocking the enzyme stearoyl CoA desaturase 1 (SCD). This enzyme converts saturated fatty acids to monounsaturated fatty acids. When SCD is blocked, the cells accumulate too many saturated fatty acids, a process referred to as lipotoxicity. Additionally, the team found that the MEK/ERK signaling pathway renders glioblastoma cells particularly vulnerable to YTX-7739, whereas the AMPK signaling pathway acts to protect glioblastoma cells and can make them resistant to the loss of de novo lipid synthesis that occurs when YTX-7739 is present.
Potential Implications for Treatment
The findings suggest that MEK/ERK and AMPK activities, which can be detected in tumor biopsies, could be predictive biomarkers to guide patient selection and stratification. Patients whose tumors have robust MEK/ERK activity would likely benefit from therapies such as YTX-7739, whereas those with high AMPK activity likely would not. Additionally, the team noted that some widely used drugs, such as the anti-inflammatory agent salicylate or the anti-diabetic compound metformin, are potent activators of AMPK and could be detrimental to the efficacy of YTX-7739 or other de novo lipid synthesis–targeting therapies.
The study provides a promising new target for the treatment of glioblastoma and could lead to more effective treatments for this aggressive form of cancer. Further research is needed to determine the efficacy of YTX-7739 in humans.
