A Phase II clinical trial funded by Cancer Research UK (CRUK) is exploring whether combination therapy with the immunosuppressive 6-MP (6-mercaptopurine, Purinethol) may offer a new option for women with advanced breast or ovarian cancer caused by faulty BRCA1 or BRCA2 genes.
Specifically, the combination of 6-MP and another chemotherapy treatment, methotrexate, could help women with BRCA-deficient cancers who are resistant either to platinum-based chemotherapy drugs such as cisplatin or to the newer PARP inhibitors.
Cell-based laboratory studies have suggested that the thiopurine class of drugs, which includes 6-MP, is effective at killing BRCA-deficient cancer cells even after they have developed resistance to treatments such as PARP inhibitors and cisplatin, CRUK says.
Launched at the University of Oxford’s Experimental Cancer Medicine Centre (ECMC), the new study aims to recruit 65 patients at 10 centres around the UK. All of these patients will have advanced breast or ovarian cancer and will be known carriers of either BRCA1 or BRCA2 gene mutations.
The Phase II trial will be co-ordinated by researchers at the ECMC and funded by Cancer Research UK and the Oxford Biomedical Research Centre.
6-MP is normally used to treat acute lymphocytic leukaemia, although it may also be prescribed for other conditions such as Crohn’s disease or ulcerative colitis.
BRCA faults
According to CRUK, around one in every 800 women in the UK carries a faulty BRCA1 gene and one in 500 has a faulty BRCA2 gene. Mutations in these genes are thought to account for about 2-5% of all breast cancer cases.
Women with the BRCA1 and BRCA2 mutation have a 45-65% chance of developing breast cancer and a 20-45% chance of developing ovarian cancer by the age of 70 years, CRUK adds.
“This study helps demonstrate the value of being able to pool subsets of patients who share specific rare faults in their tumour from a UK-wide network of Experimental Cancer Medicine Centres,” commented Dr Sally Burtles, Cancer Research UK’s director of the ECMC Network.
“This will be crucial as we move towards a new era of personalised medicine with treatments targeted according to the individual biological profile of a patient’s cancer,” Dr Burtles said.
