Ovarian cancer cells have at least four different ways to avoid being destroyed by chemotherapy, which could explain why so many treatments ultimately fail.

There have been no major changes in survival rates or treatments for high-grade serous ovarian cancer patients in the past 30 years. HGSC is the most fatal form of recurrent ovarian cancer. More than 1,300 women are diagnosed in Australia each year.

For a new study, researchers used whole genome sequencing to analyze tumor DNA samples from 91 patients with the disease.

Cell’s Hard Drive

One way the cells fight back against chemotherapy “involves breaking and rearranging big groups of genes—the chromosomes,” says Sean Grimmond, a professor in the Institute of Molecular Bioscience at the University of Queensland.

“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.”

Until now, there has been little information to guide clinicians when selecting a treatment for women whose cancer had returned, says David Bowtell, a professor from the Peter MacCallum Cancer Centre and of the Australian Ovarian Cancer Study from which many of the patient samples were obtained.

“For decades clinicians around the world have watched HGSCs shrink under attack from chemotherapy before returning aggressively months or years later,” he says. “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.”

Subtypes of Disease

The findings suggest a range of approaches are needed to overcome resistance to treatment, Grimmond says.

“We now know that not only are there many subtypes of this disease, but there are also different subtypes of resistant disease, which has 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 patient’s cancer.”

Ann-Marie Patch, et al. Whole–genome characterization of chemoresistant ovarian cancer Nature 521, 489–494 (28 May 2015) doi:10.1038/nature14410

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