Shankar Balasubramanian’s group has found a molecule, first isolated from bacteria, which can block a protein that causes breast cancer, giving an insight into how breast cancer can develop and spread.
Shankar is the Herchel Smith Professor of medicinal chemistry, based both here in the department and at Cancer Research UK’s Cambridge Research Institute. The research, published in Nature Chemistry, shows how the molecule thiostrepton ‘clamps’ the cancer-causing protein FOXM1, which stops it in its tracks.
FOXM1 is commonly found in breast cancer cells, where it attaches to specific stretches of DNA and switches on genes that regulate the growth and division of cells. It also causes tumours to spread, and triggers the growth of the blood vessels that supply the tumour with the nutrients it needs to grow and thrive. By blocking the action of this protein, it may be possible to prevent cancer from developing at an early stage, and stop it from growing and spreading.
This discovery gives chemists a starting point for designing molecules that are even better at blocking FOXM1’s ability to cause cancer than the naturally occurring molecule.
‘Before this research we weren’t aware of any natural product which could directly target a protein that controls gene activity,’ Shankar says. ‘Yet, intriguingly, a molecule in bacteria – which also has strong antibiotic effects – does this very well, switching off cancer-causing genes in breast cancer cells.
‘This naturally-occurring molecule doesn’t have all the right properties to be used as a breast cancer treatment itself. But this exciting discovery paves the way for the design of more potent and selective drugs based on the structure of thiostrepton to block the FOXM1 protein.’
The full paper is at: Nagaratna S. Hegde, Deborah A. Sanders, Raphaël Rodriguez & Shankar Balasubramanian Nature Chemistry 3, 725–731 (2011), (doi:10.1038/ nchem.1114)