As a relatively deadly type of brain cancer, the five-year survival rate of glioblastoma patients has been very low (less than 6%). The good news is that scientists at Virginia Commonwealth University have just found new applications for traditional antimalarial drugs. Combined with limited radiotherapy and Temoside chemotherapy, experiments in mice have shown the effectiveness of antimalarial drugs. Typically, glioblastomas exhibit resistance to these standard care methods, causing malignant tumors to continue to spread in the brain.
Paul B. Fisher (from Virginia Commonwealth University)
The study found that the effect depended on a new understanding of the resistance of genetic factors called Fli-1 in the treatment of glioblastoma.
Its ability to regulate the expression of aa protrusion proteins in glioblastoma (i.e., “heat shock protein” HSPB1) opens up new possibilities for intervention and restriction of the growth of malignant tumors.
Using advanced screening techniques to find drugs that inhibit Fli-1, the team at Virginia Commonwealth University found that lumefantrine, the currently approved antimalarial drug, has this unique capability.
It is reported that this alcohol can be combined with Fli-1 and inactivate it, thus terminating the expression of the genes that drive tumor formation. With this in mind, the team decided to prove it with some experimental tests.
In early in vitro studies, glioblastoma cells continue to grow with radiation and chemotherapy. However, when this alcohol is mixed, it can effectively kill cancer cells and inhibit tumor growth.
In a second mouse study, the team again found that it inhibited the growth of tumor cells, even those that had shown resistance to chemotherapy.
In addition to targeting HSPB1, the team’s work also showed that the drug had an effect on two other mechanisms — extracellular matrix (ECM) reshaping and epithelial transformation, also regulated by Fli-1 and inhibited by the drug.
Lead researcher Paul B. Fisher said these preclinical studies provide a solid basis for Fli-1/HSPB1 suppression of glioblastoma, helping to advance new approaches to treatments for diseases such as brain cancer.
Details of the study have been published in the recent lys in the Proceedings of the National Academy of Sciences (PNAS).
Originally published as Lumefantrine, an antimalarial drug, reverses radiation and temozolomide resistance inglioblastoma.