Australian researchers have identified four key ways by which one of the most common type of ovarian cancers becomes resistant to chemotherapy, a breakthrough which will better match patients with the most effective treatment.
In the largest complete DNA analysis of ovarian cancer in the world, the team led by David Bowtell from the Peter MacCallum Cancer Centre, completely sequenced the genomes of 114 samples of high-grade serous ovarian cancers donated by 92 patients.
High-grade serous ovarian cancers are responsible for 70 per cent of all ovarian cancers. Around 60 per cent of women with the condition die within five years of diagnosis.
Rosmary Goulding’s ovarian cancer has returned twice, which illustrates the problems clinicians have when treating cancer. Photo: Justin McManus
“This disease has a good response to initial treatment but then very frequently it returns,” Professor Bowtell said.
The findings, published the journal Nature on Thursday, show the cancer cells are clever. Their survival tactics include two distinct ways to repair damaged DNA so it resists the effects of chemotherapy and also “hijacking” a genetic switch that enables them to pump chemotherapy drugs out of the cell.
The research team, including scientists from the Westmead Millennium Institute, also found clusters of cancer cells could build a protective layer around them which prevented chemotherapy drugs reaching the cells.
“Mapping all the mutational mechanisms gives you an idea of how the cancer evades treatment and what treatments are less likely to work and which ones are more likely to work,” Professor Bowtell said. “It starts to introduce a rational approach to drug selection in patients.”
Professor Bowtell said the same chemotherapy drugs had been used for decades and this research provided the first insight into what was happening in patients. The findings will allow for a more tailored treatment for patients, once doctors determine the type of mutation at work.
It also has the potential to contribute to a new generation of drugs, designed with the behaviour of the cancerous cells in mind.
The samples used in the study were collected before treatment, some years later when the cancer became resistant to treatment and in the case of two women, after they died.
Retired poultry farmer Rosemary Goulding had stage three high-grade serous ovarian cancer when she was diagnosed in April 2012.
Mrs Goulding, 65, had surgery to remove tumours followed by six months of chemotherapy when she was told she was in the clear.
“The following July I got up and looked at my tummy in the mirror and thought ‘this is not right’,” the mother of three said.
Scans showed there was a tumour measuring 9 centimetres by 4 centimetres wide in her abdomen. Mrs Goulding underwent after another round of chemotherapy before returning for a check-up in August 2014, when more small tumours were detected.
“I’ve had it three times, it’s been very frustrating,” she said. “My prayer is that one day a woman will be able to walk into a doctor’s surgery and say ‘I want to have a test for ovarian cancer please’.”