Researchers identify new target for cancer therapies

New York, Sep 21: Opening up a new way to fight cancer, researchers including one of Indian-origin have found a way to target an enzyme that is crucial to tumour growth while also blocking the mechanism that has made past attempts to target that enzyme resistant to treatment.

They were able to use this finding to develop a drug that successfully inhibits tumour growth of melanoma as well as pancreatic and colorectal cancer in mice, according to a study published in the journal Cancer Discovery.

The target is an enzyme called PPT1, which controls both the mechanistic target of rapamycin (mTOR), 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.

Numerous drugs that target mTOR are approved by for cancer patients by the US Food and Drug Administration, but targeting mTOR with these currently available inhibitors turns on autophagy, thus making the tumour resistant, the study said.

"What we learned in this study is that mTOR and autophagy aren't opposed to each other as previously thought. They're actually complementary, because autophagy provides the nutrients that allow mTOR to direct growth, while mTOR shuts off autophagy when the nutrients aren't needed," said co-senior author Ravi Amaravadi, Associate Professor at Perelman School of Medicine at University of Pennsylvania in the US.

That yin and yang relationship takes place in a part of the cell called the lysosome.

"We know that autophagy is an important mechanism for cancer resistance, but there are very few ways to block it. This is the first targeted approach to inhibiting the lysosome in order to block autophagy," Amaravadi said.

The drug that makes it work is called DQ661, and it specifically targets the PPT1 enzyme that controls both mTOR and autophagy.

This study suggests drugs that target PPT1 in this way could one day improve outcomes for cancer patients.

While the approach has clear clinical benefits, researchers still need to develop these compounds into drugs that are suitable for human patients.

The researchers said that will be the focus of their efforts moving forward.