Malaria medications are effective for cancer treatment, thanks to this enzyme

WASHINTON DC: According to previous studies, anti-malarial medicine called chlororcine repurposed to treat cancer for decades, but so far no-one knew exactly what the chlororines aimed at when attacking a tumor.

Researchers from the University of Pennsylvania explained that an enzyme called PPT1 – opens a new pathway for potential cancer treatments. The results were found in the Journal of Cancer Discovery.

The team also used CRISPR / Cas9 redirection to remove PPT1 from cancer cells in the lab and found that elimination of it reduces tumor growth. They describe a potent chlorokin, known as DC661, which can benefit from this new treatment route.

“The discovery of this goal is crucial for the fact that chlorochines are currently being evaluated in clinical trials worldwide, and this knowledge basically changes the way we look at these attempts,” says the co-author of the study Ravi K. Amaravadi.

PPT1

is an enzyme that helps control both the mechanical target of rapamycin (mTOR), an important regulator for growth in cancer cells, and a process called autophagy, a built-in resistance mechanism that allows cells to survive at attack by breaking down unnecessary parts and recycling them to stay alive.

In a previous study, Penn researchers showed that these two processes work hand in hand, as autophagy provides nutrients that allow mTOR to control growth, while mTOR turns off auto-layers when nutrients are not needed.

Based on his previous work, researchers used CRISPR / Cas9 to knock out PPT1 from cancer cells to see if its removal had the same effect as chlorokin.

Researchers further showed that concept by targeting melanoma cells with DC661, which specifically targets PPT1 and produces cell death in many cell lines tested both in vitro and in vivo. It is a dimeric form of the antimalarial drug kinakrine, which means that it has two molecules of kinakrin bound together with a particular linker.

Amaravadi added that when you put the pieces together, it shows incredible promise.

“We now have a specific molecular target in cancer, as well as an effective way to achieve it,” Amaravadi said. “It not only provides a new context for current clinical trials involving hydroxyclorokine but also with the further development of these compounds against clinical drug candidates, it opens the door for key testing of our compounds or their optimized derivatives versus current chloroquines to see which ones are more effective.”