New hope for sufferers of hereditary forms of breast cancer was reported Thursday by British teams who have found a novel class of anticancer drug that may also be used in fighting other tumors. A pilot trial of a pill from the new class is about to start on women with breast cancer and, based on animal and cell studies, doctors expect it to have fewer side effects than conventional chemotherapy. In the longer term, the drug may be used as a prophylactic to cut the risk of cancer in women who have inherited a faulty gene, sparing them the need for a mastectomy.

The drug is targeted at the 2% of women diagnosed with breast cancer each year who have a hereditary form – caused by mutations in BRCA1 and BRCA2 genes. But the new strategy may also work in 20% of other forms of cancer. Groups led by Dr. Alan Ashworth, of the Breakthrough Breast Cancer Research Centre, London – working with KuDOS Pharmaceuticals – and Dr. Thomas Helleday, of Sheffield University, report in the journal Nature how they have adopted a paradoxical strategy to kill the tumors that result from these faulty genes.

The cancer genes both play a role in a key DNA repair mechanism. Faults in the genes knock this mechanism out, making it more likely that errors lead to cells multiplying out of control.

The approach advocated offers the first targeted treatment for hereditary forms of the disease.

They propose the use of a drug to knock out a second, backup DNA repair mechanism, carried out by an enzyme called poly(ADP-ribose) polymerase (PARP).

Because DNA is constantly under repair in dividing cells to enable them to survive, a drug that knocks out this backup repair mechanism kills cancer cells and leaves normal ones unscathed.

The groups have validated this idea by showing that blocking PARP slows the growth of BRCA2-deficient tumors in mice.

Dr. Ashworth is about to test a PARP-blocking drug developed with KuDOS in about 30 women with advanced disease.

He said: “This is a new therapeutic approach, centered on exploiting a specific deficiency in breast cancer cells – their Achilles’s heel.” The treatment offers a kinder alternative to conventional chemotherapy, which not only kills tumor cells but damages normal cells, causing distressing side effects such as nausea and hair loss.

Dr. Andrew Tutt, an oncologist at Guy’s Hospital in London, said: “If our laboratory findings are confirmed in the clinic, we could dramatically improve the treatment of patients with BRCA1- or BRCA2-associated cancers.” Steve Jackson, chief scientific officer of KuDOS – a privately owned oncology company – said: “The DNA repair technology behind this program has the potential to treat cancers that display similar characteristics.”