The largest complete DNA analysis of ovarian cancer in the world, published overnight in Nature, has revealed unprecedented new insight into the genetic twists and turns a deadly form of the disease takes to outsmart chemotherapy, potentially changing treatment approaches for women around the world.

Led by Professor David Bowtell from Melbourne's Peter MacCallum Cancer Centre, and in collaboration with researchers at The University of Queensland’s Institute for Molecular Biosciences (IMB), Brisbane, Westmead Millennium Institute for Medical Research, Sydney, and international colleagues, the study involved completely sequencing the genomes of 114 samples of high-grade serous ovarian carcinoma (HSC) from 92 patients — collected either at diagnosis, following successful and unsuccessful treatment, or immediately after death — to intricately investigate how cancer evolves to evade initially effective chemotherapy.

Professor Bowtell says the study revealed at least four key mechanisms by which initially vulnerable ovarian cancers go through genetic changes and become resistant to common chemotherapy.

‘In two of the mechanisms, cancer cells find a way of restoring their ability to repair damaged DNA and thereby resist the effects of chemotherapy; in another, cancer cells “hijack” a genetic switch that enables them to pump chemotherapy drugs out of harm’s way.

‘A further mechanism sees the molecular structure of the cancer tissue shift and reshape, such that sheets of “scar tissue” appear to block chemotherapy from reaching its target.

HSC accounts for 70 per cent of all ovarian cancers, and 60 per cent of ovarian cancer-related deaths, claiming approximately 80,000 women globally each year.

Professor Bowtell says until now there has been little information to guide clinicians when selecting treatment for women whose cancer has returned.

‘For decades clinicians around the world have watched HSCs shrink under attack from chemotherapy, before returning aggressively months or years later.

‘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.’

Professor Anna DeFazio, Head of the Gynaecological Oncology Research Group at the Westmead Millennium Institute and co-senior author on the paper, says the study could be practice-changing.

‘Each of our findings suggest a refined approach to drug selection in recurrent ovarian cancer, which could include bypassing drugs that are unlikely to be effective.

‘This particular view of such a complex disease has never been seen before, and we believe it will lead to more women receiving treatment better suited to their particular cancer, all over the world,’ says Professor deFazio.

Fellow co-senior author Professor Sean Grimmond from IMB, now based at The University of Glasgow’s Wolfson Wohl Cancer Research Centre, says finding sub-types of disease, but also sub-types of resistant disease, carries huge implications for designing future treatments.

‘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 woman’s cancer.’

Associate Professor Orla McNally, Director of Oncology and Dysplasia at The Royal Women’s Hospital says today's significant step forward would not have been possible without the selfless contributions of women with ovarian cancer from Melbourne and across Australia.

‘We give our thanks to the many women who provided samples for the research, including those who are no longer with us to witness this progress.

‘This discovery is now a part of their legacy, bringing us a step closer to better treatments for all women with ovarian cancer in the future.’

The study involved women from The Women's, Peter MacCallum Cancer Centre and Westmead Hospital in Australia, Hammersmith Hospital at the Imperial College of London, United Kingdom, and The University of Chicago, United States. The study was supported by funding from the National Health and Medical Research CouncilWorldwide Cancer Research (UK), Cancer AustraliaOvarian Cancer Action (UK), Ovarian Cancer Australia and the Australian Government through Cancer Australia's Priority-driven Collaborative Cancer Research Scheme.

Co-first authors on the study were Dr Dale Garsed, Dr Elizabeth Christie and Dr Dariush Etemadmoghadam from Peter Mac’s Cancer Genetics Laboratory (pictured) with Dr Ann-Marie Patch from QIMR Berghofer Medical Genomics Group and formerly from IMB.

The research was enabled by the Australian Ovarian Cancer Study (AOCS), the largest molecular epidemiological study of ovarian cancer in the world. Women with high grade serous ovarian cancer can donate tissue to research by contacting AOCS.

Media coverage

'New insight for fight with ovarian cancer', The Age, Thursday 28 May, 2015

'Ovarian cancer breakthrough', Herald Sun, Thursday 28 May, 2015

'New insight into resistance to chemotherapy in ovarian cancer', Professor David Bowtell on ABC AM, Thursday 28 May, 2015

'New ovarian cancer research'Professor David Bowtell on ABC 774, Thursday 28 May, 2015

'Ovarian cancer breakthrough'Professor David Bowtell on 3AW, Thursday 28 May, 2015

Professor David Bowtell on Ten Eyewitness News, Thursday 28 May, 2015

Professor David Bowtell on SBS World News, Thursday 28 May, 2015

Professor David Bowtell on Nine News, Thursday 28 May, 2015

View Landmark international research effort reveals how deadly ovarian cancer outsmarts chemotherapy media release