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Cancer AND bioengineering AND NOT clinical, Cancer and drug not (clinical or patient), Cancer + biomarker

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Scientists Have Identified a New Therapy Target that Has Big Implications in the Fight Against Cancer

October 18th, 2017

In a study recently published in Cancer Discovery, researchers discovered a way to target an enzyme that plays a critical role in tumor growth. Even more astonishing, this enzyme is able to block a well studied pathway that has been shown to cause cancer cells to become resistant to treatment.

PPT1 is the name of this target enzyme and it is a regulator of the mechanistic target of rapamycin (mTOR) and autophagy, a cellular process that is a cell death pathway. Both mTOR and autophagy play important roles in cancer. mTOR is a major regulator of growth in cancer cells and autophagy can act as a resistance mechanism that allows cells to survive during an attack by degrading unnecessary materials and recycling them to stay alive. Currently, there are a number of US Food and Drug Administration drugs that target mTOR and inhibit it, but that leads to activation of the autophagy pathway, thus making these tumors resistant. This recent study helps to demonstrate the previously unknown complementary effect between mTOR and autophagy. Autophagy helps to provide nutrients that allows mTOR to direct cell growth and mTOR turns off autophagy when nutrients are unnecessary.

In the past, it would require two drugs to inhibit both mTOR and autophagy processes in order to inhibit tumor growth and cancer resistance. This study has shown that DQ661, a dimeric form of the antimalarial drug quinacrine, inhibits the PPT1 enzyme that controls both mTOR and autophagy in the lysosome. Previous studies have shown that drugs hone in on the lysosome are more efficient. This is the first study to show that DQ661 can inhibit PPT1 in the lysosome, thus successfully inhibiting mTOR and the autophagic pathway. Researchers hope this study will help lead the way to develop these compounds into drugs that are suitable for human patients, and therefore has the potential to save lives.


A unified approach to targeting the lysosome's degradative and growth signaling roles (September 2017)

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