Why Do Ovarian Cancer Drugs Fail?

Research seeks to determine how cancer cells avoid chemotherapy.

Ovarian cancer cells are able to avoid death from chemotherapy through 4 different methods, according to a recent study.

Published recently in Nature, the study utilized whole genome sequencing to evaluate samples of tumor DNA from 91 patients diagnosed with high-grade serous ovarian cancer (HGSC), which is the most deadly form of the disease.

"The brave patients allowed their tumor 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," said researcher Ann-Marie Patch, MD, from QIMR Berghofer Medical Research Institute in a press release.

HGSC is a recurrent form of the disease that is able to develop resistance to standard platinum-based chemotherapy treatments that seek to damage tumor DNA beyond repair, however there have not been any significant changes in HGSC survival rates or treatments over the past 3 decades.

"For decades, clinicians around the world have watched HGSCs shrink under attack from chemotherapy before returning aggressively months or years later," lead researcher David Bowtell, of Melbourne's Peter MacCallum Cancer Centre, said in a press release. "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."

One of the methods HGSC cells use to survive is through breaking off and rearranging large groups of chromosomes.

"This is fundamentally different to other cancers where the disease is driven by smaller but more gradual changes to individual genes,” Professor Sean Grimmond, from The University of Queensland's Institute for Molecular Bioscience, said in a press release. "It is essentially shattering big chunks of the cell's hard drive and moving them around, rather than just changing bits in the files."

Due to the multiple methods the disease uses to survive, the research indicated that a variety of treatment approaches are necessary to overcome resistance.

"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," Grimmond 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."