An international collaboration shows how ovarian cancer develops resistance to chemotherapy.

The largest complete DNA analysis of ovarian cancer, to date, has been published in Nature. The paper, ‘Whole–genome characterization of chemoresistant ovarian cancer’, gives a fascinating insight into how the disease builds resistance to chemotherapy.

The study was led by Professor David Bowtell from Melbourne’s Peter MacCallum Cancer Centre, in collaboration with several international institutes. 114 samples of high-grade serous ovarian carcinoma (HSC) were collected from 92 patients. These were taken following treatment (successful or unsuccessful), or immediately after death. Sequencing these samples, exposed some of the mechanisms responsible for the genetic changes, in these cancers, that may lead to resistance.

Speaking on the study, Professor Bowtell commented, “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.”

“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.”

Dr Ann-Marie Patch, from QIMR Berghofer Medical Genomics Group and formerly from IMB, says cutting-edge technology was crucial to this turning-point in the global fight against ovarian cancer.

“By using the latest sequencing techniques we have been able to find scars from breaks in the DNA that have helped us better define the genes involved in allowing tumours to grow.

“The research team is incredibly appreciative of the many women who allowed their 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.”

Participants in the study were patients at the Peter MacCallum Cancer Centre and Westmead Hospital in Australia; Hammersmith Hospital at Imperial College London; and The University of Chicago.