Existing drugs could target smokers’ lung cancer

26 April 2012

Lung cancer cells

Image: Lung cancer cells could be targeted by a combination of existing drugs©  Cancer Research UK

Scientists at Cancer Research UK have revealed a possible new treatment for a common and aggressive form of lung cancer.

The team at the charity's London Research Institute (now part of the Francis Crick Institute), studying mice, found that combining a drug currently used for treating a heart condition with another medicine that treats a bone marrow cancer, could be used to stop tumours in non-small cell lung cancer.

The researchers looked for weaknesses in a gene called Ras, which goes wrong because of smoking. They found that faulty Ras genes rely on a second gene known as GATA2 to create tumours. The scientists found that the effect of GATA2 can be stopped in mice with non-small cell lung cancer by using a combination of drugs: Bortezomib (Velcade) - a drug for malignant myeloma, and Fasudil - used to treat Pulmonary Hypertension.

When the team looked at organs before and after treatment, they found the drugs had reduced the proportion of the lungs covered by tumours by around 99 per cent.

Dr Julian Downward, lead author from Cancer Research UK's London Research Institute, said: "The results we saw in our initial studies were extremely promising. It's very unusual to see such a striking effect - an organ affected by cancer almost completely cleared of the disease.

"It's too early to say whether this combination of drugs will be effective in patients with lung cancer but plans are underway already to test this theory in a clinical trial.

"If the trial is successful, it will be an extremely exciting step forward in the treatment of lung cancer, and potentially other types of cancer too.

"Ras is one of the most important genes in cancer, and when it goes wrong it can cause extremely aggressive cancers. Nearly a quarter of all cases of cancer are driven by faulty Ras proteins. And in some types of cancer - notably pancreatic cancer - it's more like nine out of 10 cases.

"So far we've just studied mice with lung cancer caused by faulty Ras. But by targeting the biology behind Ras, this combination of drugs holds the potential to treat a wider range of cancers."

  • The LRI scientists showed that blocking the cell's proteasome - the part of a cell responsible for breaking down proteins - and a protein called Rho kinase, stopped the activity of GATA2. This in turn stopped the growth of tumours with faulty Ras genes.
  • Bortezomib (Velcade), a drug for malignant myeloma, targets the proteasome. And a drug called Fasudil, which is used to treat a vascular condition affecting the heart called pulmonary hypertension, blocks the activity of Rho kinase.
  • The research is published in Cell. Paper: The GATA2 transcriptional network is requisite for Ras oncogene-driven non-small cell lung cancer. Kumar et al. Cell (2012), doi:10.1016/j.cell.2012.02.059.