A healthy breast consists of different cell types.

In the nucleus of the cells, you can find the DNA.

Every day, the DNA of each cell is damaged thousands of times.

If only one strand of the DNA is damaged, this can be easily repaired. PARP proteins bind to the damage and attract other proteins that repair the damage.

When damaged DNA duplicates before the damage is repaired, a double-strand break can arise.

In a healthy cell, this more severe damage can be repaired with the help of homologous recombination.

BRCA1 protein binds the loose ends of the DNA and starts to unravel the DNA strands.

Using the undamaged DNA strand as a template, the damage is then repaired.

Finally, the two strands are separated, leaving both DNA strands error-free. In patients with hereditary breast cancer, the BRCA1 mechanism does not work.

When a double-strand break arises in the cells of these patients, the DNA cannot be repaired.

The persisting damage can cause cells to die, but it can also transform a cell into a cancer cell.

This cancer cell is the start of a tumour in which all cells have the same defect. In this patient-specific treatment, an inhibitor of PARP is being used.

The inhibitor reaches the tumour via the bloodstream and inactivates the PARP proteins.

When a single-strand break arises in the DNA of the tumour cell, it can no longer be repaired.

The persisting single-strand break can transform into a double-strand break.

Because of the hereditary defect in the tumour cells, the BRCA1 protein cannot repair this damage, causing the tumour cells to die. In the surrounding healthy cells, the repair mechanism of single-strand breaks is also inactivated by the PARP inhibitor.

These cells, however, still have active BRCA1 proteins, which repair the double-strand breaks and allow the cells to survive.

As soon as the PARP inhibitor is removed after treatment, the repair of single-strand breaks is reactivated.

By that time, all tumour cells have already been killed. Towards a new treatment for breast cancer.