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Press Release

CR UK

Trigger for 'undruggable' lung cancer gene offers new treatment hope

Thursday 12 May 2011

Cancer Research UK Press Release

Cancer Research UK scientists have discovered that an enzyme called C-Raf controls a hugely important gene responsible for the development of lung cancer, according to research published in Cancer Discovery* yesterday (Wednesday).

The important gene – K-Ras – is one of the most commonly mutated genes in cancer. But it has been difficult to develop inhibitors of mutated K-Ras because of the structure of the molecule.

But now, a team based at Cancer Research UK’s Cambridge Research Institute have shown that C-Raf is needed for mutated K-Ras to encourage the growth of lung cancer.

This opens up a completely new avenue of research looking at ways to block the growth of lung cancer, bypassing the K-Ras gene.

Professor David Tuveson, lead author of the study, said: “The K-Ras gene has presented us with a difficult problem for lung cancer and other cancers where K-Ras is mutated, like pancreatic and bowel cancer. It’s known as an ‘undruggable’ gene – drugs developed to target and block the protein produced by the mutated gene have, to date, failed to do so.

“Our discovery may provide us with a solution to this problem. We now know that K-Ras can’t promote lung cancer development without the enzyme C-Raf.

“It’s an exciting result and we’ll be taking this research further to see if blocking C-Raf can be a feasible way to stop the cancer-causing effects of K-Ras.”

Dr Florian Karreth, first author of the study, said: “Under normal conditions, B-Raf seems to be the major player. So we were surprised to find that instead K-Ras depends on C-Raf to initiate lung cancer.”

The researchers used genetic techniques to get rid of two enzymes – C-Raf and B-Raf – in mice and in lung cells in the laboratory. They found that when B-Raf was knocked out, it had no effect on whether K-Ras was able to turn normal cells into cancer cells. But when C-Raf was removed, cancer development was prevented.

Mutations in Ras genes are seen in around 30 per cent of all tumours and K-Ras is the most common type of Ras mutation.

Dr Lesley Walker, director of cancer information at Cancer Research UK, said: “As we’re learning more about the genetics of cancer, we’re starting to uncover just how complex it is.

“The discovery of K-Ras was an important milestone but it turned out to be more difficult to target than we initially thought. This study offers us a way to target the gene through the ‘back door’.”

Ends

For media enquiries please contact the Cancer Research UK press office on 020 3469 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Reference

  • C-Raf is required for the initiation of lung cancer by K-RasG12D. Karreth et al. Cancer Discovery. 11 May 2011.
 
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