Scimex: Australian-led research has identified the different ways ovarian cancer
is able to develop a resistance to chemotherapy. The authors developed
the largest whole-genome analysis of high-grade serous ovarian cancer to
date, a disease that accounts for the majority of all ovarian cancer
deaths. Ovarian
cancer cells can lock into survival mode and avoid being destroyed by
chemotherapy, an international study reports. Pr
Sean Grimmond, from The University of Queensland said ovarian cancer cells had at least four different ways to avoid being destroyed by platinum-based chemotherapy treatments.
"One
way involves breaking and rearranging big groups of genes – the chromosomes,"
Professor Grimmond said.
"This
is fundamentally different to other cancers where the disease is driven by
smaller but more gradual changes to individual genes.
"It
is essentially shattering big chunks of the cell's hard drive and moving them
around, rather than just changing bits in the files."
The
research used whole genome sequencing to analyse tumour DNA samples from 91
patients with high-grade serous ovarian cancer (HGSC).
HGSC
is the most fatal form of ovarian cancer, a disease for which there are more
than 1300 diagnoses in Australia each year.
Professor
Grimmond said it was a recurrent form of cancer that often developed resistance
to standard platinum-based chemotherapy treatments that aimed to damage tumour
DNA beyond repair.
There
have been no major changes in survival rates or treatments for HGSC patients in
the past 30 years.
Professor
Grimmond, now based at The University of Glasgow's Wolfson Wohl Cancer
Research Centre, and Professor David Bowtell from Melbourne's
Peter MacCallum Cancer Centre led the research
team with Professor Anna deFazio
from Sydney's Westmead Millennium
Institute for Medical Research. They collaborated with a team of cancer
researchers, including Dr Ann-Marie Patch from QIMR Berghofer Medical Research Institute, formerly from IMB,
to interpret the sequencing results.
Professor Bowtell, Head of Peter Mac's Cancer Genomics Program
and of the Australian Ovarian Cancer Study (AOCS) from
which many of the patient samples were obtained, said until now there had been little information to guide clinicians
when selecting a treatment for women whose cancer had returned.
"For decades clinicians around the world have watched
HGSCs shrink under attack from chemotherapy before returning aggressively
months or years later," he said.
"By completely sequencing the cancers, sampled at
different stages of disease, for the first time we can map their evolution
under the selective pressure of chemotherapy and begin work on better
interventions."
Dr Patch, formerly from IMB and now at QIMR
Berghofer's Medical Genomics Group, acknowledged the support of patients and
their families who had participated in the study
"The
brave patients allowed their tumour samples to be collected so that we can find
out what happens to the cancer cells after treatment and will allow us to work
towards better treatments for women in the future," she said.
Professor Grimmond said the research indicated a range
of approaches would be needed to overcome resistance to treatment.
"We
now know that not only are there many sub-types of this disease, but there are
also different sub-types of resistant disease, which has huge implications for designing
future treatments," he said.
"We
really need to continue to write the atlas for this complex disease and get
more sophisticated about the amount of drug we give, when we give it, and the types
and combinations of treatments in relation to each patient's cancer."
The
study's results are published today in Nature.