Lung cancer discovery confirms drug target's potential

In collaboration with the Press Association

A protein called Rac1 plays a key role in the development and spread of lung cancer, according to a research group in the US.

The finding adds to growing evidence that drugs targeting Rac1 could one day prove effective treatments.

Rac1 is a protein involved in controlling when and how cells move around the body. Faults that cause it to become hyperactive, or present in high quantities, have previously been linked to several types of cancer, including melanoma and lung cancer.

The researchers showed in mice that when the protein is overactive it can trigger a normal process called epithelial-mesenchymal transition, (EMT) that renews organs and other tissues, by switching cells from one state to another.

Cancer cells can hijack this process and use it to spread from the initial tumour to other sites around the body.

Researchers believe that turning off EMT could help stop cancers from spreading.

The researchers also showed that a protein called matrix metalloprotease 3 (MMP3) could switch on Rac1, and that this process could be accelerated by chemicals found in cigarette smoke.

Commenting on the research, Professor Owen Sansom, deputy director of Cancer Research UK's Beatson Institute, and an expert on Rac1, said the work added further weight to the protein's importance in cancer.

"This is an important new piece in a complex jigsaw puzzle," he said.

"It adds to the growing evidence that the Rac1 protein is hyperactive in several types of cancer - notably lung cancer and melanoma. And it backs up the idea that targeting Rac1 with drugs would be an effective way to treat these diseases.

"Excitingly, there are several experimental drugs currently being developed that can target this protein.

"Given the urgent need for new treatments for skin and lung cancer, we sincerely hope that these can be brought to human trials quickly and successfully."

Lead researcher Dr Radisky, from the Mayo Clinic in Florida, said: "Our study points to EMT as a key step in lung cancer progression during the earliest stages of cancer development.

"Normal cells recognise when they are dividing too rapidly and turn on programmes that block inappropriate cell division. Here we found that early-stage lung cancer cells switch on EMT in order to bypass these controls."

The research is published in Science Translational Medicine.

Copyright Press Association 2012

References

  • Stallings-Mann, M.L., Waldmann, J., Zhang, Y., Miller, E., Gauthier, M.L., Visscher, D.W., Downey, G.P., Radisky, E.S., Fields, A.P. & Radisky, D.C. (2012). Matrix Metalloproteinase Induction of Rac1b, a Key Effector of Lung Cancer Progression, Science Translational Medicine, 4 (142) 142ra95. DOI: 10.1126/scitranslmed.3004062