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Scientists discover way to target rare breast cancer mutation

UK scientists have identified a drug to target a rare breast cancer mutation that helps drive the disease in around 900 of the 50,000 new cases of breast cancer diagnosed in the UK each year. 

The cutting-edge research was carried out by Breast Cancer Campaign Scientific Fellow Dr Rachael Natrajan and colleagues*, based at The Institute of Cancer Research, London. The study was funded through a Scientific Fellowship grant by Breast Cancer Campaign, worth over half a million pounds, and also received funding from Breakthrough Breast Cancer.

The scientists performed a re-analysis of the genetic data of nearly 1,300 tumours, as they set out to investigate whether faults in genes that control ‘RNA splicing’ play a role in the development of breast cancer.

RNA (ribonucleic acid) is responsible for delivering the “instructions” found in our DNA from the centre (nucleus) of the cell to the rest of the cell. When there are faults in the way RNA is put together, or ‘spliced’, this can influence what messages the RNA delivers, potentially telling cells to grow when they shouldn’t, which can lead to them becoming cancer cells that grow out of control. 

The study found that a mutation, in the gene SF3B1, occurred in 1.8% of breast cancers the researchers looked at – equivalent to around 900 of the 50,000 new cases of breast cancer diagnosed in the UK every year. The mutation was more common in rare subtypes of breast cancer called ‘papillary’ and ‘mucinous’ breast cancers, which together make up around 5% or less of breast cancers diagnosed each year. The scientists also discovered that the mutation was associated with ER-positive breast cancer, a type of the disease that grows in response to the hormone oestrogen, and that tumours with this mutation had errors in the way their RNA was spliced.

In the same project, the scientists identified a drug that targets these mutations via a particular protein that controls the way the RNA is spliced in the mutant cells.

“Our findings indicate that, although rare, SF3B1 mutations cause cells to splice their genetic instructions differently. They could be driving the growth of some breast cancers, and present a new target for treatments that could potentially be tested in clinical trials”, says Dr Rachael Natrajan, Breast Cancer Campaign Scientific Fellow at the  Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research, London.

Katherine Woods, Senior Research Communications Manager at Breast Cancer Campaign, said: “There is still so much we don’t know about how cells become cancerous and what makes the disease progress for each patient. The pioneering work of our Scientific Fellow Dr Natrajan has led to an invaluable discovery in our understanding of the biology of breast cancer. This brings us one step closer to our ambition that by 2030, what causes different breast cancers to grow and progress will be identified, enabling us to select the best treatment for every patient.”

The scientists are now working to validate the results in other models and identify even more effective drugs to target this new kind of mutation with. Dr Natrajan and colleagues are also hoping to identify further types of mutations that can be targeted with the same approach.

The study, ‘SF3B1 mutations constitute a novel therapeutic target in breast cancer’ is published today, Wednesday 26 November, in the Journal of Pathology.

The research is published as leading charities Breakthrough Breast Cancer and Breast Cancer Campaign announce that they intend to merge to create the UK’s largest dedicated research charity committed to ending breast cancer. Both charities believe the merger will lead to more funds being invested in research, a more comprehensive programme of research overall into all areas of breast cancer prevention and treatment and will create a single voice for all those dedicated to ending breast cancer, helping ensure that the benefits of research reach patients quicker. The new charity is expected to launch in Spring 2015.

Support from Asda’s Tickled Pink, which has now raised over £40m, has enabled Breast Cancer Campaign to fund Dr Natrajan’s Scientific Fellowship.

*The first three authors on this paper, Drs Sarah L. Maguire, Andri Leonidou and Patty Wai, contributed equally to the study and should be equally acknowledged in any reporting.

Maguire et al. SF3B1 mutations constitute a novel therapeutic target in breast cancer. The Journal of Pathology. 2014. DOI: 10.1002/path.4483


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