Landmark international research has revealed how deadly ovarian cancer outsmarts chemotherapy and other drug treatments.
The largest complete DNA analysis of ovarian cancer in the world, published 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, the study involved completely sequencing the genomes of 114 samples of high-grade serous ovarian carcinoma from 92 patients. The samples were 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”.
High-grade serous ovarian carcinoma (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”.
Have you or a loved one been touched in some way by ovarian cancer?