A research project funded by the Bone Cancer Research Trust has identified two proteins that when targeted can switch off the TBTX gene (also known as brachyury). TBXT is largely responsible for the uncontrolled growth of chordoma cells. This discovery could lead to new treatment options for patients.

The TBXT gene is expressed for a brief period of time in human development, when it helps create an early form of the human skeleton. After 12 weeks, when its biological task is completed, the TBXT gene is switched off.

If TBXT becomes reactivated in adulthood, it can contribute to uncontrolled growth of cells and the development of cancer. Switching off the TBXT gene is therefore an attractive approach to find new therapies for cancer and chordoma specifically.

Genes can be silenced by chemical modification of DNA and the proteins that it wraps around, causing DNA to fold tightly, and making some parts inaccessible (gene inactive).

Particular proteins (enzymes) are responsible for making these chemical modifications, and for reversing them; therefore targeting these enzymes might provide a way to silence the TBXT gene, when it is inappropriately activated in cancer cells.

Dr Lucia Cottone and Dr Adam Cribbs found that when two enzymes, known as KDM6A and KDM6B were restricted, the TBTX gene was silenced, causing the chordoma cells to die off. Dr Lucia Cottone, Research Fellow and lead author of the study said:

By screening more than 90 drugs, we have been able to identify a compound that switches off the TBXT gene and kills chordoma cells.

The findings suggest that targeting KDM6A and KDM6B could provide a route for finding new treatment options for chordoma, a cancer for which survival rates have barely improved for decades.

The TBXT gene is also inappropriately switched on in other tumour types – suggesting that targeting TBXT could also become a potential therapeutic option for a wider range of cancers.

To find out more about Dr Cottone's and Dr Cribbs research project, please click below.

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