Researchers trial new drug for women with hereditary breast and ovarian cancer

Cancer Research UK

A CANCER RESEARCH UK-funded trial of a new drug for patients with advanced breast or ovarian cancer due to inherited gene faults has been launched at the Oxford Experimental Cancer Medicine Centre (ECMC) at the University of Oxford.

The trial, led by a team based at the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, is looking at a drug called 6MP, which is already used to treat leukaemia and is often given alongside another chemotherapy drug called methotrexate.

Earlier studies involving cells grown in the laboratory suggest that a class of drugs called thiopurines, which includes 6MP, are effective at killing cancer cells lacking BRCA - a gene which significantly increases risk of breast and ovarian cancer - even after they have developed resistance to treatments like PARP inhibitors and cisplatin.

This trial is one of a growing number looking at matching patients to the most appropriate treatment based on their genetic makeup and that of their cancer – an approach known as personalised medicine.

If successful the results will pave the way for a larger phase III trial, which could in future lead to an important extra treatment option for the 15 out of every 100 women with breast and ovarian cancers caused by faults in BRCA1 or BRCA2 genes.

Trial leader Dr Shibani Nicum, a gynaecology specialist based at the Oxford ECMC, and a researcher in Oxford University’s Department of Oncology, said: “PARP inhibitors are a powerful new class of drugs developed specifically to target tumours caused by BRCA 1 and BRCA2 faults, but drug resistance remains a problem. We hope that the very encouraging results we have seen in early laboratory studies involving 6MP will lead to increased treatment options for these patients in the future.”

Trial participant Suzanne Cole, 54, from Newbury, has a strong history of ovarian cancer in her family, with her sister, mother and grandmother all having been diagnosed with suspected cases of the disease at a relatively young age. But it wasn’t until many years later, after she herself was diagnosed with cancer, that doctors were able to trace the cause of this back to a BRCA1 mutation in her family.

She said: “I was diagnosed in 2009 and initially had surgery then chemotherapy. I was then told about the trial and I went away and studied the information. The doctors were able to answer all my questions and then I agreed to sign up. I’m happy to be a part of this work as it could help others by moving treatments forward."

Professor Mark Middleton, director of the Oxford ECMC at Oxford University, said: “It’s exciting to see drugs being developed for specific groups of patients who share the same underlying genetic faults in their cancer. Targeted treatments are at the cutting edge of cancer care and we’re proud to be involved in bringing such drugs a step closer to the clinic.”

Dr Sally Burtles, Cancer Research UK’s director of the ECMC Network, said: “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. 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.”

For more information on the trial, please visit www.cancerhelp.org.uk or call the Cancer Research UK cancer information nurses on 0808 800 4040.

ENDS

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Notes to Editor

BRCA1 and BRCA2

  • Around 1 in 800 women in the UK carry a faulty BRCA1 gene and 1 in 500 carry a faulty BRCA2 gene.
  • Mutations in these genes are thought to account for around 2-5 per cent of all breast cancer cases.
  • Women carrying the BRCA1 and BRCA2 mutation have a 45-65 per cent chance of developing breast cancer, and a 20-45 per cent chance of developing ovarian cancer, by the age of 70.
  • Genetic testing for faulty BRCA genes is available on the NHS for women with a very strong family history.

Treatment for BRCA-deficient cancers

Cells lacking BRCA1 or BRCA2 are less able to repair DNA damage. This makes them more sensitive to platinum-based chemotherapy drugs such as cisplatin – which work by causing double-stranded DNA breaks - and also PARP inhibitors – a newer class of drugs which prevent cells lacking BRCA from being able to repair damaged DNA. PARP inhibitors have shown huge promise in clinical trials but, as with most drugs, resistance can develop meaning some women can stop responding.