BRCA2 – From Bench to Bedside and Back Again

The ICR and The Royal Marsden NHS Foundation Trust work in partnership to produce high quality basic research and translational studies, with the aim of developing better treatments for the benefit of cancer patients worldwide. We often characterise our approach to cancer research as ‘bench to bedside and back again’, meaning that there should be a constant, two way interaction between laboratory scientists and clinicians.

The clinical observation that breast cancer can run in families led scientists to search for the genetic basis of this phenomenon. In 1995, ICR researchers isolated the BRCA2 breast cancer gene and 10 years later, the MARIBS trial results were reported. This study showed that, for young women who were at high risk of breast cancer and had a high probability of carrying BRCA1/BRCA2 mutations, screening by magnetic resonance imaging (MRI) was much better than mammography.

Meanwhile, researchers were working to show that the protein encoded by the BRCA2 gene has a role in DNA repair. They found that cells lacking BRCA2 function are highly sensitive to drugs that inhibit poly-ADP-ribose polymerase (PARP), an enzyme which plays a key role in another DNA repair pathway. These observations led to PARP inhibitors being tested in clinical trials. In 2009, the ICR and The Royal Marsden, in collaboration with other scientists published the results of these trials, which showed that PARP inhibitors have remarkable impact in breast, ovarian and prostate cancer patients.

Outcomes like this are what defines ‘bench to bedside and back again’. An issue that was originally defined by clinicians was followed by extensive laboratory work, which resulted in improved screening procedures and a new therapy of great potential.