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Antimalarial Drug Proven Very Effective In Killing Tumor Cells

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Antimalarial Drug Proven Very Effective In Killing Tumor Cells 

Researchers at the Perelman School of Medicine, the Abramson Cancer Center, and the School of Arts and Sciences at the University of Pennsylvania, have discovered a new way to fight cancer. Scietists have developed a new drug, called Lys05, which proved effective in killing cancer cells in mice.

It seems that the mechanism of action of the new drug consists of blocking the process of recycling in cancer cells, thus interfering with autophagy. Recently, studies have shown that autophagy can be one of the targets that can be used to stop tumor growth. Autophagy, ie self eating, is a protective process that allows cells to survive during starvation. During starvation, autophagy allows cells to degrade proteins and other molecules and use them as an energy source. Autophagy is a genetically programmed process mediated by lysosomes, intracellular organelles. In conditions of starvation, a double membrane vesicle is formed that includes particles to be “eaten”, and then it merges with a lysosome.

Ravi K. Amaravadi, MD, assistant professor of Medicine, and colleagues, demonstrated in previous studies the role of hydroxychloroquine, an antimalarial drug in cancer treatment. Hydroxycloroquine proved useful not only as an antimalarial drug, but also in autoimmune diseases such as Sjogren’s syndrome, rheumatoid arthritis, lupus, etc. Also hydroxycloriquine by inhibiting the activation of dendritic cells from skin, reduces inflammation. Regarding cancer, it seems that hydroxycloroquine  can reduce the autophagy of  cancer cells. In addition, this drug enhances the effect of chemotherapy. However, hydroxycloroquine can not always be used as doses proven effective against cancer are too high. Therefore, Ravi K. Amaravadi teamed up with Jeffrey Amaravadi Winkler, PhD, the Merriam Professor of Chemistry, to develop a new molecule, derived from cloroquine, which can be used in cancer treatment.

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Chloroquine

Starting from the basic molecule of hydroxycloroquine (cloroquine), researchers have synthesized a new molecule, called Lys05, which has antitumor effects in mice at non-toxic doses. Chemical synthesis and biological evaluation are described in detail in the early edition of the Proceedings of the National Academy of Sciences. Unlike hydroxycloroquine, this new molecule was proven to be effective in reducing tumor growth in the absence of other therapies.

“This single-agent anti-tumor activity suggests this drug  may be even more effective in patients than hydroxychloroquine.” Amaravadi said. He added that Lys05 acts predominantly in cancer cells and on  healthy cells has little or no effect. He also added that Lys05 Amaravadi should be the subject of further studies before being tested on humans.