‘DNA tags’ could guide treatment for advanced ovarian cancer

15 October 2013

Ovarian cancer, ultrasound image

Image: Ovarian cancer, ultrasound image©  CAMAL, ISM/SCIENCE PHOTO LIBRARY

Chemical 'tags' on DNA in patients' tumours could help doctors decide the type of chemotherapy women with advanced ovarian cancer should receive, according to a new study by scientists from Imperial College London and the Institute of Cancer Research, London.

The DNA tags could be used to assess whether patients will benefit from their current treatment or if other drugs should be tried, as well as indicating whether their cancer is likely to come back.

The Cancer Research UK scientists found these tags - known as epigenetic markers - at genes known to be linked with ovarian cancer.

The researchers looked for associations between particular tags and features of the disease, including how well a patient responded to chemotherapy and how quickly their cancer returned after the first round of treatment.

They looked at the epigenetic markers in around 150 ovarian cancer tumours from women in the UK and then confirmed what they discovered in over 300 ovarian tumours from a world-wide study.

The markers are located at regions of DNA called CpG islands, which behave like switches controlling genes by turning them on and off through a process known as DNA methylation. Previous studies have shown that when this process malfunctions it can lead to cancer development and affect how tumour cells respond to chemotherapy.

The team found 29 markers that identified how quickly a patient's tumour came back after standard treatment. Of these, epigenetic markers at three genes - NKD1, VEGFB and PRDX2 - were found to be most strongly associated with how well a patient's tumour would respond to carboplatin-based chemotherapy, the front-line treatment, and how long a patient would be in remission.

In addition, some of the markers identified were at genes that may be targets for another type of chemotherapy drug, bevacizumab (Avastin), which is known to improve survival of ovarian cancer patients when used in combination with carboplatin-based chemotherapy. These epigenetic markers may help to select patients who will particularly benefit from this treatment.

Professor Bob Brown, of Imperial College London and Institute for Cancer Research, said: "Our study shows that epigenetics is important for ovarian cancer and we may be able to tailor chemotherapy according to the epigenetic characteristics of a woman's ovarian tumour.

"These findings also mean we could be able to predict how likely it is that a patient's tumour will come back and find ways to stop the tumour recurring or developing resistance to chemotherapy."

Dr Kat Arney, of Cancer Research UK, said: "Genetic markers are already used in some cancers, such as breast, to help doctors decide which treatments to give. But, we still don't know much about epigenetic markers, or their particular role in ovarian cancer.

"Understanding how ovarian cancers differ epigenetically might help doctors in the future to decide what treatments to give. And we hope that studies like this could lead to more improvements in treatment in the future, for people affected by all types of cancer."

The paper, Promoter CpG Island Methylation of Genes in Key Cancer Pathways Associates with Clinical Outcomes in High Grade Serious Ovarian Cancer, is published in Clinical Cancer Research.

  • A Cancer Research UK team at Imperial College London and the Institute of Cancer Research, London has found chemical 'tags' on ovarian cancer tumours that could help doctors decide on treatment for women with advanced disease. 
  • The tags are known as epigenetic markers. Epigenetics refers to modifications to DNA that can affect whether genes are switched on or off. The tags were found at genes known to be linked to ovarian cancer and indicated how well a patient was likely to respond to treatment and how likely a tumour was to come back after chemotherapy. 
  • The study was part-funded by Ovarian Cancer Action, Imperial Experimental Cancer Medicines Centre, Imperial Biomedical Research Centre and Imperial Cancer Research UK Centre.