Antimalarial drug boosts glioblastoma treatment
The drug, called lumefantrine, may increase the success rate of radiation and chemotherapy treatments for a extreme kind of brain cancer.
Glioblastoma multiforme (GBM) can be an especially aggressive type of cancer that's difficult to treat.
With available therapies, the 5-year survival rate for folks with GBM is 5.6%. Doctors now have no way of stopping the recurrence of the condition.
Experts estimate that malignant brain tumors and cancers of the central nervous system - 81% which are glioblastomas - kill 241,000 people each year worldwide.
New research finds that lumefantrine, a drug approved by the meals and Drug Administration (FDA) to combat malaria, can enhance the effectiveness of the primary drug used to take care of GBM.
The study’s principal investigator, Prof. Paul Fisher, chair of the Virginia Commonwealth University’s Department of Human and Molecular Genetics, explains that his team had been investigating whether approved pharmaceuticals may help weaken GBM’s resistance to chemotherapy.
“Our studies uncovered a fresh potential application of the antimalarial drug just as one therapy for [GBM] resistant to the standard of care, entailing radiation and temozolomide.”
The findings come in in the journal Proceedings of the National Academy of Sciences of america of America.
Overcoming GBM’s resistance
The current standard of care for treating GBM is radiation coupled with chemotherapy, especially temozolomide. Together, they are able to marginally extend the life expectancy of individuals with GBM, but the disease can often be resistant to the treatment.
The authors of the study found that adding lumefantrine to in vitro treatment of glioblastoma cells with radiation and temozolomide killed the cancer cells and suppressed their new growth.
Moreover, the combined approach had this influence on glioblastoma cells that would otherwise have already been resistant to treatment, as well as to the ones that would have been sensitive to it.
In vivo experiments further confirmed the effect. The researchers transplanted human GBM in to the brains of the mice and, again, the combo of radiation, temozolomide, and lumefantrine proved successful at killing both sensitive and resistant glioblastoma cells and suppressing further growth.
Heat shock protein B1 and Fli-1
Lumefantrine apparently inhibits a newly determined genetic element, Fli-1. This, researchers say, is involved in the development and progression of cancer and can promote glioblastoma’s resistance to radiation and temozolomide.
Genetic and molecular approaches revealed that Fli-1 regulates the expression of heat shock protein B1 (HSPB1).
This protein is common in glioblastoma tumors and may contribute to the development of GBM - including that resistant to treatment - since it can regulate extracellular matrix remodeling and epithelial-mesenchymal transition, according to the study’s authors.
It was the visit a Fli-1 inhibitor that finally led the researchers to lumefantrine.
Lumefantrine is toxic to cells, but selectively so, which is why this is a good applicant as a cancer therapy. The authors say that the easily available drug could be easily repurposed for use in glioblastoma treatment.
Where this research may lead
The researchers are encouraged by their findings.
“These preclinical studies provide a solid rationale for Fli-1/HSPB1 inhibition with lumefantrine as a potential novel approach for glioblastoma management,” says Prof. Fisher.
“Identification of drugs like lumefantrine from FDA-approved therapeutic agents and from uncommon sources provides opportunities to broaden the breadth and versatility of current therapeutic regimens for [GBM] patients.”
- Prof. Paul Fisher
It may also come out that GBM is merely the start for lumefantrine, suggests Prof. Fisher, who adds, “Today's results may have broader implications than just treating glioblastoma.”
As Fli-1 also appears at elevated levels in other cancers, including melanoma, ovarian cancer, and breast cancer, lumefantrine may potentially play a role in their treatment. However, further research into lumefantrine’s cancer-fighting potential will be required.
Source: www.medicalnewstoday.com
