Brain Cancer: Study Shows Lumefantrine Enhances Current Protocol To Treat Glioblastoma Multiforme(GBM)
Source: Brain Cancer May 27, 2020 3 years, 10 months, 4 weeks, 1 day, 18 hours, 20 minutes ago
Brain Cancer: Researchers from Virginia Commonwealth University Massey Cancer Center and Institute of Molecular Medicine (VIMM) have reported that lumefantrine, an FDA-approved drug used to treat malaria has demonstrated effectiveness to enhance existing treatment protocols to treat Glioblastoma multiforme (GBM), an aggressive form of cancer in the brain that is typically fatal.
The research findings were published in the journal
Proceedings of the National Academy of Sciences.
https://www.pnas.org/content/early/2020/05/13/1921531117
Current standard of care involving radiation and temozolomide, an anti-cancer chemotherapy, can marginally extend the lives of patients with glioblastoma multiforme brain tumors.
However resistance of GBM to these therapies is a frequent occurrence.
Also, the five-year survival rate of GBM patients treated with the standard of care is less than 6 percent, and no current therapies prevent recurrence.
The medical researchers have focused on discovering FDA-approved drugs and more uncommon agents that could potentially help counteract glioblastoma's resistance to and effectiveness of treatment.
Dr Paul B. Fisher, the principal investigator told Thailand Medical News, "Our research uncovered a new potential application of the antimalarial drug as a possible therapy for glioblastoma multiforme resistant to the standard of care entailing radiation and temozolomide."
Significantly, lumefantrine can inhibit a genetic element involved in cancer development and progression, Fli-1, which controls resistance of glioblastoma multiforme to radiation and temozolomide.
In vitro studies the team found that incorporating lumefantrine while treating glioblastoma killed cancer cells and suppressed tumor cell growth. This occurred in both glioblastoma cells sensitive to and those that otherwise would be resistant to radiation and temozolomide.
During vivo studies in animal models (using mice containing a transplanted human glioblastoma multiforme in their brains), lumefantrine inhibited tumor growth caused by both therapy-sensitive and therapy-resistant glioblastoma cells.
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The significant discovery of lumefantrine's ability to neutralize the body's resistance to radiation and chemotherapy came through genetic and molecular approaches that identified the new genetic element "Fli-1" as an important genetic element controlling resistance to therap
y. This discovery became a focal point of the current research.
The study team found that "heat shock protein B1," also known as HSPB1, is prominent in glioblastoma tumors, and its expression is regulated by Fli-1. Innovative screening strategies for Fli-1 inhibitors identified lumefantrine as a prospective agent that could bind to Fli-1, inactivate it and thereby suppress expression of important genes regulating growth, survival and oncogenicity (ability to cause tumors) of glioblastoma multiforme.
Furthermore two key processes essential for cancer invasion and spread known as extracellular matrix (ECM) remodeling and epithelial mesenchymal transition (EMT) are important factors that regulate glioblastoma's ability to respond and resist radiation and chemotherapy. Those two processes are regulated by Fli-1 and are inhibited by lumefantrine.
In order to help treat glioblastoma, the medical researchers will further explore other means to counteract therapy resistance induced by Fli-1.
Dr Fisher added, "These preclinical studies provide a solid rationale for Fli-1/HSPB1 inhibition with lumefantrine as a potential novel approach for glioblastoma management. 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 glioblastoma multiforme patients."
Interestingly beyond glioblastoma, an elevated expression of Fli-1 can be seen in cancers such as melanoma, ovarian cancer, breast cancer and others.
The medical researchers suggested that blocking the cancer-promoting effects of Fli-1 might help other cancer patients as well.
Dr Fisher concluded "The present results may have broader implications than just treating glioblastoma as it could be used for a wide range of cancers as well.)
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