According to previous studies, anti-malaria drugs known as chloroquines have been repurposed to treat cancer for decades, but until now no one has known exactly what chloroquines were aimed at when they attack growth. Now, researchers from the University of Pennsylvania have explained that an enzyme called PPT1 – opens a new pathway to potential cancer treatments. The findings appeared in the Journal of Cancer Discovery. The team also used CRISPR / Cas9 gene-editing to remove PPT1 from cancer cells in the laboratory and found that this elimination slows tumor growth. They listed a strong chloroquine, known as DC661, that could utilize the new treatment pathway.
"The discovery of this target is critical because chloroquines are currently evaluated in clinical trials all over the world, and this knowledge fundamentally changes the way we look at these experiments," said lead author of the study, Amravadi.
PPT1 is an enzyme that helps control both the mechanistic goal of rapamycin (mTOR), the primary regulator of growth in cancer cells, as well as a process called autophagy, a built-in resistance mechanism that allows cells to survive when under attack by breaking unnecessary parts and recycling them to stay alive.
In previous research, the researchers showed that both processes work hand in hand when autophagy provides the nutrients that allow mTOR to direct growth, while mTOR closes the autophagy when the nutrients are not needed.
Building off their previous work, researchers used CRISPR / Cas9 to knockout PPT1 cancer cells to see if its removal had the same effect as chloroquine.
Researchers have further demonstrated that the concept by targeting melanoma cells with DC661, which targets specific PPT1 and produces cell death in many cell lines tested both in vitro and in vivo. It is a daimeric form of the drug Quinacrine antalalaria – meaning that there are two molecules of quinacrine tied together with a special linker.
Amaravadi added that when you put the pieces together, it shows an amazing promise.
"We now have a specific molecular target for cancer as well as a strong way to reach it," Amaravadi said. "It not only provides new context for current clinical trials involving hydroxychloroquine but also, with the further development of these compounds towards clinical drug candidates, it opens the door for head-to-head testing of our compounds or their optimized derivatives compared to current chloroquines to see which effective More ".
(This story was not edited by the NDTV team and is automatically generated from the consolidated update).