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.