The blood vessels supplying aggressive brain tumors have receptors that could allow the creation of a new type of anti-cancer drug. The treatment would be encapsulated in nanoparticles and would have the particularity of depriving carcinogenic cells of the energy necessary for their growth and multiplication. It might even cause carcinogenic cells to self-destruct. These advances are the result of research carried out by scientists from the Universities of Nottingham and Duke.
Malignant gliomas are the most common brain tumours. Very aggressive, they leave affected patients with an average lifespan of only 4.6 months, which can go up to 14 months when a treatment combining chemotherapy and radiotherapy is followed.
“Brain tumors can be very difficult to treat because many effective drugs or nanoparticles in the laboratory cannot cross the blood-brain barrier behind which most of them are located. It is therefore vital to find a new way to treat them,” said Dr Ruman Rahman from the University of Nottingham School of Medicine, one of the study’s co-authors.
According to data collected from 169 patients including 133 children and published in Pharmaceutics, vessels supplying gliomas show an elevated level of low-density lipoprotein (LDL) receptor. These lipoproteins transport cholesterol in the blood and bring it to the cells. Researchers assume that cancer cells use the nutrients provided by lipoproteins to mobilize the energy necessary for their growth and multiplication. “The key now is to use drugs and nanoparticles that will target these receptors, and cut off the energy supply to cancer cells,” affirms Dr Ruman Rhaman.
David Needham, Professor of Translational Therapy at the University of Nottingham’s School of Pharmacy also participated in the research. The scientist is working on the development of new formulas of niclosamide, a common inhibitor that cuts off the energy supply to cells. Used, among other things, as a vermifuge for more than 60 years, the molecule kills the worms present in the digestive tract by stopping their energy supply. Niclosamide could be modified to treat certain diseases including cancer.
“Niclosamide not only targets the production of energy in the cell, but also sets in motion other processes that induce apoptosis (programmed cell death). Now that we know that tumor cells have LDL receptors, which we hypothesize use to fuel their growth and expansion, we can work to modify drugs so that they target cancer cells and rob them of their energy. Since cancer cells feed off LDL, our strategy is to make the drug look like their food.” said David Needham.
The scientist, who is also a professor of mechanical engineering and materials science at Duke University, worked with a team from this university on a technology called Brick to Rocks technology (B2RT). It has enabled them to manufacture pure prodrug nanoparticles that allow drugs to be delivered precisely to their place of action, and only activated once they have arrived at their destination. They have already succeeded in developing a drug called ‘niclosamide stearate prodrug therapeutic’ (NSPT) which can stop the formation of metastases in dogs suffering from osteosarcoma. Some of the animals studied in a small study have recovered from their cancer.
“This technology is now ready to be applied to other cancers and Nottigham is ideally placed to develop it with the expertise of the Childhood Cancer Tumor Research Centre. The next step will be to test this technology on brain tumors in animals, and if the results are promising, move on to patients as quickly as we can while ensuring their safety,” said Prof Needham.
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