Protein May Explain Chemo Resistance in Patients With BRCA2 Mutations
Researchers have discovered a protein that may lead to a new way to prevent resistance and improve outcomes for patients whose cancers have a BRCA2 mutation. The findings were reported in Molecular Cell (http://www.cell.com/molecular-cell/fulltext/S1097-2765(17)30457-4).
RADX is a DNA-binding protein that helps repair and ensure accuracy of DNA copies during cell division. BRCA2 mutations disrupt these repair functions, increasing patients’ risk for breast, ovarian, prostate, and pancreatic cancer as well as melanoma.
When a patient with a BRCA2 mutation initially begins treatment, the mutation actually enhances the effect of chemotherapies such as cisplatin or olaparib. However, the cells can acquire a secondary mutation that restores normal BRCA2 function and causes chemotherapy resistance. For example, 25% of patients with BRCA2 ovarian cancer will become resistant to cisplatin within six months.
The researchers hypothesized that RADX may be key to overcoming treatment resistance and prolonging five-year survival. Additional studies are needed to determine clinical applicability.