According to previous research, anti-malaria drugs known as chloroquine have been re-aborted to treat cancer for decades, but so far no one knew exactly what chloroquine was when they attacked a tumor. Now researchers at the University of Pennsylvania have explained that an enzyme called PPT1 – opens up a new path for potential cancer treatments. The results appeared in the Journal of Cancer Discovery. The team also used the CRISPR / Cas9 gene edition to eliminate PPT1 from cancer cells in the laboratory and found that eliminating them decreased tumor growth. They described a powerful chloroquine, known as DC661, which can take advantage of this new route of treatment.
"The discovery of this objective is critical because chloroquins are being evaluated in clinical trials around the world and this knowledge fundamentally changes the way we look at these trials," said Ravi K. Amaravadi, co-author of the study.
PPT1 is an enzyme that helps control the mechanistic purpose of rapamycin (mTOR), an important regulator of the growth of cancer cells, as well as a process called autophagy, an integrated resistance mechanism that allows cells to survive when they are attacked by breaking it Unnecessary parts and recycle them to keep alive.
In a previous study, Penn researchers have shown that these two processes work from hand to hand, since autophagia provides nutrients that allow mTOR to grow directly, while mTOR disables autophagia when nutrients are not needed.
From their previous work, the researchers used CRISPR / Cas9 to eliminate PPT1 from cancer cells to see if their elimination had the same effect as chloroquine.
The researchers have demonstrated even more than the concept directed to 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 antimalarial pharmacological quinacrine, which means that it has two quinacrine molecules linked to a special bond.
Amaravadi added that when putting the pieces together, it shows an incredible promise.
"Now we have a specific molecular objective in cancer, as well as a powerful way to reach it," said Amaravadi. "Not only does it provide a new context for current clinical trials involving hydroxychloroquine, but also, with the subsequent development of these compounds for candidates for clinical drugs, it opens the door to head-to-head tests of our compounds or their optimized derivatives in front To the current chloroquine, see what is most effective. "
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