Research conducted at the University of Nottingham has revealed that cancer cells with faulty BRCA genes can be killed by blocking a key DNA damage-repair enzyme called APE1.
Scientists developed and tested small molecules that block APE1 and stop the enzyme from repairing DNA in breast, pancreatic and cervical cancer cells with faults in BRCA1 or BRCA2 genes.
"The study provides the first evidence that APE1 is an important new target for personalised cancer treatment. Not only could these molecules provide a basis for new drugs to treat cancers with faulty BRCA genes - especially breast and ovarian cancer - but they could help 'soften up' cells from many cancer types to boost the effect of radiotherapy and chemotherapy," said Srinivasan Madhushan, a researcher at the University said in a statement.
The BRCA genes control a separate and major DNA repair pathway. Cells with damaged BRCA1 or BRCA2 have a faulty 'repair kit'. This allows damaged cells to accumulate faults and multiply indiscriminately - which increases the risk of developing cancer, especially related to the ovaries and the breasts.
However, too much damage of that sort could also lead to the death of the cell. Blocking APE1 in these BRCA-deficient cells effectively blocks two repair routes at once and kills the cancer cells.
This particular technique is already in use, with a new class of drugs called PARP inhibitors. These prevent cells fixing faults in BRCA-deficient cells by blocking PARP, a key enzyme in the same repair pathway as APE1.
"With up to ten per cent of all breast cancers thought to result from faulty BRCA1 and/or 2 genes, new treatments for these patients could possibly help up to 4,800 of the women diagnosed with the disease in the UK each year," said Baroness Delyth Morgan, the Chief Executive of the Breast Cancer Campaign.
Meanwhile, APE1, like PARP, is essential for carrying out a type of DNA damage repair - removing and correcting faulty DNA components - but has a more specific role in this repair process compared to the PARP enzymes.
"This promising new target may lead to even more specific drugs capable of delivering a knock-out double blow to cancer cells, leaving healthy cells unharmed - so potentially causing fewer side effects," said Steven Jackson, a DNA damage repair expert.
The research was presented on Monday, at the National Cancer Research Institute (NCRI) in Liverpool.