Leicester experts map structure of lung cancer culprit protein

Posted by er134 at Mar 25, 2014 07:10 AM |
University of Leicester researchers have discovered the molecular structure of a protein which causes an aggressive type of lung cancer

Leicester experts have uncovered the structure of a protein which causes an aggressive type of lung cancer – and the findings could help doctors to predict who will benefit from a specific lung cancer treatment, while saving other patients from receiving it unnecessarily.

The research was led by Dr Richard Bayliss (pictured), from our Department of Biochemistry and Professor Dean Fennell, of our Department of Cancer Studies and Molecular Medicine. They were looking at a form of the disease – known as ALK lung cancers – which account for around four per cent of cases.

These lung cancers have a fault where two different genes become locked together. This gene fusion forms a souped-up version of a protein which then becomes an engine, driving the cancer to grow very fast and spread rapidly.

But, importantly these cancers rely on this engine to survive so blocking the protein could kill the lung cancer.

Using x-ray crystallography, the researchers were able to develop a clear picture of the shape of one half of the souped-up protein. Crucially, some of the shapes are unstable and need help from another protein to work. This assistant protein can be blocked by drugs known as Hsp90 inhibitors. By stopping this helper protein, the unstable, souped-up proteins can no longer work and the cancer cells die.

But the researchers have found that for around one third of patients with ALK lung cancer, the structure of the protein uncovered by the researchers is much more stable and is resistant to the Hsp90 inhibitors.

The researchers are currently collecting data and samples from a clinical trial to find out if their lab findings hold true and can be used to predict which lung cancer patients will respond to the drug.

The new research was published in the Proceedings of the National Academy of Science on Monday, March 24, and was funded by Cancer Research UK.