How malaria medication is able to fight cancer

Anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one knew exactly what they target when they attack a tumour.

Researchers have identified the target as an enzyme called PPT1, which is highly expressed in most cancers and is associated with poor treatment outcomes.

The researchers used CRISPR/Cas9 gene editing scissors to remove PPT1 from cancer cells in the lab and found that eliminating it slows tumour growth.

PPT1 is an enzyme which controls both the mechanistic target of rapamycin (mTOR), a major regulator of growth in cancer cells, as well as a process called autophagy, which is a built-in resistance mechanism that allows cells to survive when under attack, by breaking down unneeded parts and recycling them to stay alive.

In a previous study, the researchers showed these two processes work hand-in-hand: Autophagy provides the nutrients that allow mTOR to direct growth, while mTOR shuts off autophagy when the nutrients aren't needed.

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Building off their previous work, the researchers used CRISPR/Cas9 to knock out PPT1 from cancer cells to see if its removal had the same effect as a chloroquine.

"The edited cells look like they have been treated with a drug, and grow significantly slower than the unedited cells," said co-senior author Ravi K Amaravadi.

The team further proved the concept by targeting melanoma cells with DC661, a potent chloroquinone they developed, which specifically targets PPT1 and produces cell death in many cell lines.

DC661 is a dimeric form of the antimalarial drug quinacrine - meaning it has two molecules of quinacrine bound together with a special linker.

This dimeric form is more effective at slowing the growth of cancer cells in mice than the monomeric chloroquines currently under study in clinical trials.

The findings were published in Cancer Discovery, and are expected to pave way for new cancer treatments. - Science Daily