New discovery can improve breast cancer treatment
It has been known for the last decades that mutations in the BRCA2 gene result in increased risk of developing breast cancer. The mutations are hereditable and the increased risk is passed on from mother to daughter. Researchers at BRIC, University of Copenhagen, have now revealed a new important function of BRCA2. The new knowledge can be used to improve breast cancer treatment. The results are published in the journal EMBO Reports.
BRCA2 stops cancer development
Breast cancer is the most prevalent cancer among women - In Denmark approximately 4000 new patients are diagnosed per year. Between 5 to 10 percent of these cases are hereditable, and mutations in BRCA2 are some of the most common drivers of this disease.
"BRCA2 protects against cancer development. Our new results shows that BRCA2 stops the growth of cells with damaged DNA," says Associate Professor Claus Storgaard Sørensen, Group Leader at BRIC.
"BRCA2 functions as a brake in a car - when damage occurs to the DNA, a brake stops the cells in order for the damages to be repaired," Claus Sørensen says.
Our body's functions are dependent upon constant renewal of the cells through cell division. At each cell division, a large machinery makes sure that the DNA is copied correctly. The machinery stops cells from dividing if damage occurs to the DNA-code, allowing for the damage to be repaired. This is crucial, as cells with damaged DNA can develop into cancer cells if they are allowed to divide in an uncontrolled manner.
The Sørensen research group has obtained the results using new technology where they screen known cancer genes for new roles.
"We exposed the cells to radiotherapy, which damage the DNA. We saw immediately that cells without BRCA2 behaved differently than other cells. They could divide despite the DNA damage," says postdoc Tobias Menzel, who has been the driving force behind the laboratory experiments.
Patients with BRCA2 mutations respond better to radiotherapy
In addition to explaining why BRCA2 mutation increases the risk of breast cancer, the results also have potential to improve breast cancer therapy.
"Actually, the results are quite surprising as they also show that cells with BRCA2 mutations are more sensitive towards radiotherapy than cells without such mutations," says Claus Sørensen.
The results thereby indicate that breast cancer patients with BRCA2 mutations will respond better to radiotherapy than patients without BRCA2 mutations. Thus, mutations in BRCA2 can likely be used as a marker, prior to selection of therapy for individual patients.
The explanation to why cells with BRCA2 mutations are more sensitive is that radiotherapy induces so extensive DNA damage that the cells cannot survive without repairing the damages. Normal cells will stop dividing and attempt to repair the damages, whereas cancer cells with BRCA2 mutations will divide without repairing the DNA damages, resulting in death of the cancer cells.
The next step for the Sørensen research group is to examine which of the known BRCA2 mutations found in breast cancer patients that allows for damaged cells to divide and thereby can be used as markers indicating the use of radiotherapy. In addition, the researchers will elucidate the biological mechanism making BRCA2 able to prevent damaged cells from dividing.
Original paper: Menzel at al., EMBO Reports, June 2011
BRCA2 mutations increase sensitivity towards radiotherapy. The treatment induce so extensive DNA damage that the cells can only survive if the damages are repaired. However, in contrast to normal cells, cancer cells with BRCA2 mutations divide without repairment of the damage, resulting in death of the cancer cells. Figure: Katrine Sonne-Hansen.