Study published in Nature showed that BRCA2 develops a secondary mutation that restore its DNA-repair ability.
A team of researchers identified a new mechanism that explains why some recurrent ovarian tumors become resistant to treatment with commonly used platinum-based chemotherapy drugs.
BRCA2 works to repair damaged DNA. Inherited mutations in this gene disrupt that ability, which increases the risk of ovarian and breast cancer. At the same time, such mutations also make cancer cells more vulnerable to DNA-damaging agents such as cisplatin and carboplatin. While ovarian tumors initially respond well to platinum-based chemotherapy, eventually between 70% and 80% of advanced-stage ovarian cancer patients develop a resistance to these drugs.
The researchers found that, when exposed to cisplatin, some ovarian cancer cells develop secondary mutations on their BRCA2 gene that restore the gene’s ability to repair DNA. This restoration of gene function then makes the cancer cells resistant to chemotherapy.
The researchers suspect they may be able to generalize their findings regarding secondary mutations in BRCA2 to other DNA-repair genes such as BRCA1, which may help explain drug resistance to a variety of cancers.
The team included scientists from Fred Hutchinson Cancer Research Center, University of Washington, Women’s Cancer Research Institute, and the Mayo Clinic. The study is described in the online February 10 issue of Nature.
