Now we know how chloroquine targets cancer cells

New research has uncovered an enzyme that chloroquine targets in cancer treatment. For decades after chloroquines stopped being the first-line drug for treating malaria, the medicine was repurposed for cancer treatment. But no one knew what exactly cholorquines target until now. Researchers from the the Abramson Cancer Center of the University of Pennsylvania say they […]

New research has uncovered an enzyme that chloroquine targets in cancer treatment.

For decades after chloroquines stopped being the first-line drug for treating malaria, the medicine was repurposed for cancer treatment.

But no one knew what exactly cholorquines target until now.

Researchers from the the Abramson Cancer Center of the University of Pennsylvania say they have identified that target – an enzyme called PPT1.

The team also removed PPT1 from cancer cells in the lab and found that eliminating it slows tumour growth.

The finding opens up new pathway for cancer treatment. They have already detailed a potent chloroquine, known as DC661, that can take advantage of this new treatment pathway, according to their findings published in Cancer Discovery.

“The discovery of this target is critical because chloroquines are currently being evaluated in clinical trials all over the world, including here at Penn, and this knowledge fundamentally changes the way we look at those trials,” said the study’s co-senior author Ravi K. Amaravadi, MD, an associate professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania.

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

Previous studies show both processes work hand-in-hand: autophagy provides the nutrient that allow rapamycin to grow, while rapamycin shows off autophaby when nutrients are not needed.

The researchers knocked out PPT1 from cancer cells to see if removing it had the same effect as a chloroquine.

“The edited cells look like they’ve been treated with a drug, and they grow significantly slower than the unedited cells,” Amaravadi said. “We also compiled data from existing databases and found PPT1 is both highly expressed in most cancers and also associated with poor outcomes.”