Scientists uncover how a 'master regulator' protein contributes to cancer spread

In collaboration with the Press Association

New detail about how a protein called mTOR controls the spread of cancer has been uncovered by US scientists.

The findings, published in the journal Nature, could explain why some older cancer drugs that target mTOR have been less effective than expected.

Crucially, the research also hints that newer drugs currently in trials could be better at preventing cancer spread.

The team, based at the University of California, San Francisco, used a method called 'ribosome profiling' to uncover a network of genes controlled by mTOR.

They discovered how mTOR influences one of the final stages of genes 'translating' into proteins - a process that involves tiny molecular machines known as ribosomes.

They then showed in a mouse model of human prostate cancer that tumours treated with a newer mTOR inhibitor called INK128 did not spread. The newer drug also had a strong effect on human prostate cancer cells.

INK128 is already in clinical trials for different types of cancers.

The mTOR protein is a master regulator of how and when cells make other proteins. It helps healthy cells sense nutrient levels and controls their growth and metabolism.

But this process goes awry in many cancers, and mTOR 'programmes' cells to divide uncontrollably, invade surrounding tissues and spread (metastasise) to other parts of the body.

"Many human cancers show hyperactivation of this pathway," said Professor Davide Ruggero, an author of the study.

But until now no-one knew how overactive mTOR affected the production of other proteins in a way that led to cancer, he added.

"We are now discovering that, during tumour formation, mTOR leads to metastasis by altering the synthesis of a specific group of proteins that make the cancer cells move and invade normal organs."

Several compounds that block mTOR, such as the drug rapamycin, have already been tested in trials for treating various forms of cancer such as prostate cancer - but they have not been as effective as hoped. But this new research suggests a clear reason why such drugs have failed.

Thorsten Hagemann, a Cancer Research UK expert based at Barts Cancer Institute, said the work was "very interesting", and an excellent example of how new DNA sequencing technologies are driving an increasingly detailed understanding of cancer.

He added: "We've known for some time that mTOR has a major role in cancer, but trials of drugs that inhibit this protein have been disappointing.

"This work shows mTOR could still be a valuable treatment target, and that it's possible to develop more sophisticated ways to block its cancer-promoting activity."

The fact that the researchers were able to use an mTOR inhibitor to 'reprogram' the genetic machinery behind cancer spread was fascinating, he added, and the work could have implications beyond just prostate cancer.

"It will be some time before this work makes it from the lab bench to routine clinical use, but it's a great example of how knowledge of cancer's inner machinery can uncover new strategies to beat the disease."

Copyright Press Association 2012

References

  • Hsieh, A. et al. (2012). The translational landscape of mTOR signalling steers cancer initiation and metastasis Nature DOI: 10.1038/nature10912